Ovicidal and larvicidal properties of curcumin synthetic analogs against Caenorhabditis elegans and Meloidogyne exigua

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M. Ubiali de Lima, Lucas de Lima Paula, Matheus Zago, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7242730/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Control methods for plant-parasitic nematodes encompass preventive strategies, such as the use of healthy seedlings and the implementation of conservation agriculture practices, in addition to chemical and biological nematicides. The most widely used nematicides are organophosphates and carbamates. However, the development of new nematicides has been limited, with only a few products introduced to the market. This study aimed to assess in vitro nematicidal properties of curcumin ( 1 ) and a series synthetic monoketone curcuminoid analogs ( 2–23 ) against the model nematode Caenorhabditis elegans and Meloidogyne exigua , a significant pest in coffee plantations across Brazil. An initial screening at 50 µM revealed that curcumin ( 1 ) and its more stable analog, curcumin A ( 2 ), were ineffective. In contrast, curcuminoid 3 induced 100% paralysis of C. elegans L3/L4 larvae. Curcuminoids 19 and 20 exhibited partial activity, paralyzing 75% and 55% of the larvae, respectively. EC 50 assessments indicated that curcuminoid 3 was highly potent against both L3/L4 larvae and adults of C. elegans (EC 50 90 µM. All tested synthetic monoketone curcuminoid analogs successfully inhibited egg hatching. The results demonstrated the potential of synthetic monoketone curcuminoid analogs as promising nematicide agents, particularly in inhibiting egg hatching. These findings enhance our understanding of the biological effects of curcuminoids and open new avenues for developing effective strategies to control plant-parasitic nematodes, providing valuable tools for agricultural pest management. Curcuminoids Caenorhabditis elegans Meloidogyne exigua nematicide ovicidal Introduction Coffee is the world's most widely consumed caffeine-containing beverage, surpassed only by tea and water in global consumption (Rai et al. 2024 ). Among the 130 recognized species in the Coffea genus, Coffea arabica L. (Arabica coffee) and Coffea canephora Pierre ex A. Froehner (Robusta coffee) are the most extensively cultivated (Guyot et al. 2024 ). In the first eight months of 2024, Brazil exported coffee to 138 countries, with the United States and Germany as the primary importers (Cecafé 2025 ). As the world’s leading coffee producer and exporter, Brazil’s Arabica production is projected to reach 99.9 million 60-kg bags, accounting for 56.7% of global supply (Cecafé 2025 ). Between January and September, Brazil set a record by exporting 36.428 million bags, generating US $ 8.451 billion in revenue (Cecafé 2025 ; Santana et al. 2021 ). However, coffee production faces substantial challenges, including water scarcity and pest infestations—particularly from plant-parasitic nematodes (root-knot nematodes), which can reduce global coffee yields by approximately 15% and impact Brazil’s production by up to 20% (Pinto 2019 ; Venzon 2021 ). The root-knot nematodes (RKN) of the genus Meloidogyne , particularly M. exigua , M. incognita , and M. paranaenses , are highly detrimental to coffee cultivation in Brazil. These nematodes have a complex life cycle that begins with egg hatching, followed by larval migration to plant roots, where they induce gall formation (Carneiro & Cofcewicz 2008 ; Santos et al. 2018 ). These galls hinder water and nutrient absorption, weakening the plant and reducing productivity (Afridi et al. 2024 ). Nematode spread can occur via infected seedlings, runoff, or contaminated agricultural equipment, underscoring the importance of preventive management strategies (Lamelas et al. 2020 ; Matiello et al. 2024 ; M. F. A. Santos et al. 2018 ). On the other hand, Caenorhabditis elegans —a free-living nematode frequently used as a model organism in biological research—is maintained easily in laboratory settings and shares key biological traits with plant-parasitic nematodes like Meloidogyne (Corsi et al. 2018 ; Cortese et al. 2006 ). These similarities, which include conserved metabolic pathways and sensory neuroanatomy, allow C. elegans to serve as a model for studying parasitic nematodes (Rengarajan & Hallem 2016 ; Shivakumara et al. 2019 ). Control methods for plant-parasitic nematodes include preventive practices, such as utilizing healthy seedlings and implementing conservation agriculture techniques, alongside chemical and biological nematicides (Matiello et al. 2024 ). The most widely used chemical nematicides are organophosphates and carbamates. However, the development of new nematicides has been limited, with few products introduced to the market since 1970s(Cao et al. 2022 ). Certain plants, particularly those of the genus Curcuma , are recognized for their resistance to nematodes and other pests. Curcumin, a key compound in Curcuma longa , (Kocaadam & Şanlier 2017; Kotha & Luthria 2019 ) has demonstrated notable biological activities, including nematicidal effects. However, its application is limited due to its low bioavailability and rapid degradation (Anand et al. 2007 ; Singh et al. 2011 ). Synthetic analogs of curcumin, modified in the central carbon chain, offer improved stability and enhanced antiparasitic activity (Carapina da Silva et al. 2019 ; Chauhan et al. 2018 ; Rai et al. 2020 ; Souza et al. 2021 ; Vieira et al. 2024 ; Zorofchian Moghadamtousi et al. 2014 ). Although curcumin’s efficacy has been documented against Ascaridia galli , its effects on RKN, specifically within the genus of the genus Meloidogyne , remain unreported (Bazh & El-Bahy 2013 ). This study aims to evaluate the nematicide effects of curcumin ( 1 ) and a range of synthetic monoketone curcuminoid analogs ( 2–23 ) on C. elegans and M. exigua in vitro . Material and methods Drugs The synthesis methods of all test compounds ( 2–23 ) have been previously described in the literature (Vieira et al. 2018 ). Levamisole, used as a positive control for the C. elegans assays, and curcumin ( 1 ) were obtained from Sigma-Aldrich (St. Louis, MO, USA). For the M. exigua assays, fluensulfone (Nimitz®, ADAMA, Asdode, Israel) served as the positive control. All tested compounds had a purity of at least 95%, except curcumin, which was 80% pure. Nematodes cultures The wild-type C. elegans strain (Bristol N2) was maintained on nematode growth medium (NGM) agar plates inoculated with Escherichia coli OP50 at 20°C, following established according to standard protocols (Stiernagle 2006 ). Synchronous populations were prepared for all experiments using a standard bleaching method (Stiernagle 2006 ). Meloidogyne exigua population used in the experiments was obtained from coffee plants in Ribeirão Corrente, SP, Brazil (20°32’30’’ S and 47°25’11’’ W), and identified by α-esterase phenotypes (Carneiro & Cofcewicz 2008 ). This population was maintained on Coffea arabica ‘Mundo Novo’ under greenhouse conditions. Approximately 4 days prior the bioassays, eggs and J2 juveniles were extracted from soil and roots following the Boneti and Ferraz method (1981). The extracted nematodes were quantified using a Peters’ slide and subsequently used as inoculum. Screening of compounds against C. elegans at L3/L4 and adult stages of, and EC 50 determination For the screening of compounds against C. elegans , 10 worms at the L3/L4 stage were placed into each well of a 96-well plate containing 150 µL of S medium. 31 Compounds 1 – 23 , previously dissolved in dimethyl sulfoxide (DMSO) (Sigma-Aldrich), were added at a concentration of 50 µM. The nematodes were incubated at 20°C for 24 h, and motility changes were assessed visually using a Zeiss Axiovert 40 C inverted microscope (Zeiss). All nematodes were categorized as either mobile or immobile (paralyzed, defined as showing no movement for 1 minute of observation) (Luo et al. 2018 ). Control groups included nematodes in S medium with 0.1% DMSO (the negative control) and a positive control group treated with levamisole (Sigma-Aldrich) at 24 µM. Each experiment was conducted in duplicate and repeated twice for consistency. To determining the 50% effective concentration (EC 50 ), experiments were conducted as previously above with the compounds that caused paralysis in more than 50% of the nematodes in the screening, and evaluated at concentrations ranging from 6.25 to 100 µM, while levamisole was evaluated at concentrations from 6.25 to 50 µM. In vitro nematocidal assay against M. exigua J2 larvae The nematicide activity of compounds 1 , 2 , 3 , 19 , and 20 was evaluated against M. exigua J2 larvae following the protocol by Silva et al. ( 2019 ). The compounds were dissolved in DMSO and tested at concentrations ranging from 6.25 to 100 µM, while fluensulfone (Nimitz®) was tested at final concentrations ranging from 3.75 to 60 µg.mL − 1 (equivalent to 12.85 to 205 µM) (Pacule 2020 ). Approximately 10 J2 larvae were placed in each well of a 24-well plate along with the compounds and incubated in the dark at 28°C for 72 h. After this period, the solution was replaced with mineral water for an additional 24 h to confirm mortality by observing immobility. J2 larvae that remained immobile, straightened, or exhibited abnormal morphology were classified as dead (Franzener et al., 2007 ). Control groups, nematodes were incubated in mineral water containing 0.1% DMSO (negative control) or fluensulfone (Nimitz®) at 62.2 µg.mL − 1 (positive control). Evaluation of egg hatching for C. elegans and M. exigua The eggs from C. elegans and M. exigua were obtained following the protocols by Stiernagle ( 2006 ), and Boneti & Ferraz ( 1981 ), respectively. Approximately 50 µL of an egg suspension (~ 50 eggs) was added to each well of a 96-well plate, containing M9 buffer for C. elegans or mineral water for M. exigua . Compounds 1 , 2 , 3 , 19 , and 20 , dissolved in DMSO, were tested at concentrations ranging from 6.25 to 100 µM. C. elegans eggs were incubated at 20°C for 24 h, while M. exigua eggs were kept at room temperature in the dark and observed for up to 10 days. Following incubation, L1 larvae counts were conducted visually using a Zeiss Axiovert 40 C inverted microscope. Control groups included eggs in M9 buffer with 0.1% DMSO ( C. elegans ) or in mineral water with 0.1% DMSO ( M. exigua ). For M. exigua , fluensulfone (Nimitz®) at 62.2 µg.mL − 1 (213.23 µM) served as a positive control, while levamisole was excluded due to its lack of ovicidal activity (Albuquerque 2019 ; Pacule 2020 ). Statistical analysis Results were expressed as mean ± standard deviation (SD) of three independent experiments conducted in triplicate and converted to percentage values. Experimental data were analyzed for normality using the Shapiro-Wilk test, followed by one-way analysis of variance (ANOVA) with significance assessed by the Dunnett test. EC 50 values were determined from the dose-response inhibition curve using nonlinear regression, with 95% confidence intervals calculated for each EC 50 value. All statistical analyses were performed using GraphPad Prism version 8.0 for Windows (GraphPad Software, USA). Results Curcuminoid 3 exhibits nematicidal activity against C. elegans L3/L4 larvae An initial screening was conducted with curcumin ( 1 ) and the synthetic monoketone curcuminoid analogs (2–22) at 50 µM for 24 h against C. elegans L3/L4 larvae. As showed in Table 1 , curcumin ( 1 ) and curcumin A ( 2 ), a more stable analog, did not exhibit any nematicide effect. In contrast, analog 3 emerged as the most potent compound, resulting in 100% larval mortality after the incubation period. Compounds 4 and 5 were inactive during screening. Besides compound 3 , analog 19 also showed significant activity, paralyzing 75% of the larvae, while compound 20 demonstrated moderate efficacy with 55% motor unresponsiveness (Table 1 ). Levamisole, used as a positive control at 24 µM, caused complete larval lethality. Based on these findings, curcuminoids 3 , 19 , and 20 were selected for further evaluation to determine their EC 50 values over a concentration range of 6.25 to 100 µM (Table 2 ). Curcumin ( 1 ) and curcumin A ( 2 ) were also included in this assessment for structural comparation with monoketone analogs. Table 1 After 24 h of exposure to curcumin ( 1 ), curcumin A ( 2 ), and the analogs 3 , 19 , and 20 , compound 3 demonstrated strong nematicidal potential, achieving an EC 50 value < 6.25 µM for both C. elegans L3/L4 and adult stages (Table 2 ). This potency exceeded that of the positive control, levamisole, which presented an EC 50 of 10.50 µM (3.45–26.04 µM) for the L3/L4 stage and 14.99 µM (7.22–29.53 µM) adult worms. Curcumin ( 1 ) and curcumin A ( 2 ) showed no nematicidal activity at the tested concentrations. Regarding to compounds 19 and 20 exhibited promising nematicidal activity, with an EC 50 of approximately 33 µM for both L3/L4 and adult C. elegans (Table 2 ). Table 2 Determination of the effective concentration 50 (EC50) against Caernohabditis elegans and Meloidogyne exigua following incubation with curcumin and its synthetic monoketone curcuminoid analogs EC 50 a (µM) Compounds C. elegans L3/L4 larvae (24 h) C. elegans adult (24 h) M. exigua J2 (24 h) M. exigua J2 (72 h) 1 > 100 > 100 > 100 > 100 2 > 100 > 100 > 100 > 100 3 < 6.25 100 97.69 (81.78–117.3) 20 33.76 (24.87–41.87) 34.81 (27.94–43.90) 97.62 (81.43–116.8) 91.65 (77.67-111.65) Positive control b 10.50 (3.45–26.04) 14.99 (7.22–29.53) 117.58 (96.65–137.80) 92.58 (78.01-113.56) a EC 50 : effective concentration required to paralyse 50% of the worms. b Positive control: levamisole (24 µM) for C. elegans and fluensulfone (Nimitz®) (12.85 a 205 µM) for M. exigua . Values in parentheses represent the 95% confidence interval. Table 2 Curcuminoid analogs exhibit moderate nematicidal activity against J2 M. exigua The concentrations required for nematicide activity against J2 M. exigua were consistently higher than those needed for C. elegans at all time points (Table 2 ). After 24 h and 72 h of incubation, curcumin ( 1 ), curcumin A ( 2 ), evaluated for structural comparation, exhibited an EC 50 values higher than100 µM. In contrast, the curcuminoid analogs 19 and 20 displayed EC 50 values equal to or exceeding 91 µM. Compound 3 demonstrated moderate efficacy against J2 larvae after 24 and 72 h exposure, with EC 50 values of 93.05 µM (79.87–114.0 µM) and 57.62 µM (50.56–66.47 µM), respectively. For the positive control, fluensulfone ((Nimitz®), the EC 50 values were found were to be > 100 µM and 92.58 µM (78.01-113.56) for 24 h and 72 h, respectively. Curcuminoid analogs inhibit egg hatching in C. elegans and M. exigua. The use of ovicidal assays in anthelminthic drug discovery represents a promising strategy for disrupting the life cycle of parasitic worms by preventing egg hatching (Easland et al. 2023 ; Schärer et al. 2023 ). To evaluated the ovicidal potential of compounds, eggs from C. elegans and M. exigua were incubated with various concentrations of the compounds and assessed for hatching after 24 h or monitored over a 10-day period, respectively. As shown in Table 3 , compounds 1 and 2 didn’t exhibit any effect on the eggs of C. elegans . In line with the nematicidal assays, curcuminoid 3 completely inhibited egg hatching in C. elegans at concentrations ranging from 100 µM to 12.5 µM, with a significant reduction in hatching observed at 6.25 µM. Compounds 19 and 20 also demonstrated significant reductions in egg hatching for C. elegans , with 23.00 ± 2.64%, and 34.00 ± 4.00% of eggs hatching at 100 µM and 50 µM, respectively. Additionally, 20 exhibited 43.67 ± 4.72% and 46.33 ± 5.85% hatching rates at these concentrations. It is noteworthy that levamisole, the nematicide drug used for C. elegans , does not exhibit any ovicidal effect on the eggs of the worm. Table 3 Evaluation of Caernohabditis elegans and Meloidogyne exiguas egg hatching after exposure to curcumin and synthetic monoketone curcuminoid analogs % Hatched eggs 6.25 µM 12.5 µM 25 µM 50 µM 100 µM C- a C + b C. elegans c 1 85.00 ± 13.23 86.67 ± 11.55 88.00 ± 8.54 89.33 ± 6.11 84.00 ± 7.00 100.00 ± 0.00 - 2 93.00 ± 5.77 90.00 ± 10.00 88.00 ± 8.54 90.00 ± 6.00 87.67 ± 9.50 - 3 21.67 ± 2.88 * 0.33 ± 0.57 * 0.33 ± 0.57 * 0.66 ± 1.15 * 0.00 ± 0.00 * - 19 92.67 ± 3.05 75.67 ± 5.13 62.33 ± 3.21 43.67 ± 4.72 * 23.00 ± 2.64 * - 20 100.00 ± 0.00 100.00 ± 0.00 100.00 ± 0.00 46.33 ± 5.85 * 34.00 ± 4.00 * - M. exigua d 1 90. 00 ± 11.55 85.00 ± 10.00 88. 00 ± 9.79 76.70 ± 6.60 72.70 ± 8.50 100.00 ± 0.00 0.00 ± 0.00 * 2 0.00 ± 0.00 * 3 0.00 ± 0.00 * 19 0.00 ± 0.00 * 20 0.00 ± 0.00 * a C-: negative control; M9 buffer with 0.1% DMSO for C. elegans and mineral water with 0.1% DMSO for M. exigua . b C+: positive control; fluensulfone (Nimitz®) at 62.2 µg/mL (213.23 µM) for M. exigua; Levamisole was not included as a positive control for C. elegans due to its lack of ovicidal activity. c Eggs incubated with compounds for 24 h. d Eggs incubated with compounds for 10 days. Data expressed as mean ± SD from three different experiments. * p < 005 indicates statistically different difference from the negative control group. “–“ denote data not evaluated. Table 3 In M. exigua , the monoketone curcuminoid analogs 2, 3, 19 , and 20 inhibited egg hatching by 100%, demonstrating strong ovicidal activity (Table 3 ). For comparison, the positive control fluensulfone (Nimitz®) also inhibited 100% of egg hatching, but only at 213 µM-twice the highest concentration tested for the curcuminoid compounds. Discussion RKN of the genus Meloidogyne are sedentary parasites that have evolved complex strategies to penetrate and migrate through plant roots. They utilize different feeding mechanisms, targeting either cortical or vascular cells to support their development and reproduction (Perrine-Walker 2019 ). These adaptations place them among the most destructive agricultural pests, causing significant reductions in crop yields, with coffee being particularly impacted (Tapia-Vázquez et al. 2022 ; Thi Phan et al. 2021 ). Among Meloidogyne species, M. exigua is especially harmful to coffee production, predominantly in Central and South America, where it is the most prevalent nematode in coffee-growing regions. The economic impact of RKN is substantial, with global annual losses estimated to exceed USD 170 billion (Elling 2013 ). Although nematode control typically includes various pest management strategies, such as short-term nematicide applications, many traditional nematicides have been banned in recent years due to environmental and health risks (Forghani & Hajihassani 2020 ). Additionally, nematodes have developed resistance to these conventional treatments, underscoring the urgent need for new nematicides with minimal risks to human and the environment (Nguyen et al. 2022 ). Research on Meloidogyne species has been greatly informed by the model organism C. elegans , as these two organisms share substantial genomic similarities, indicating conserved developmental and biochemical pathways (Nguyen et al. 2022 ). C. elegans is frequently used in studies investigating nematicide due to its small size, well-characterized genome, ease of maintenance, short life cycle, and efficient reproduction (Fuentes et al. 2022 ; Tapia-Vázquez et al. 2022 ). In this research, we investigated the nematicide and ovicidal effects of curcumin ( 1 ) and a series of synthetic monoketone curcuminoid analogs against C. elegans and M. exigua . Curcumin ( 1 ), the major compound of Curcuma longa L. (turmeric), along with its structurally similar analog, curcumin A ( 2 ), showed no nematicidal activity against either organism. Shen et al.(2013) demonstrated that curcumin ( 1) could increase the mean lifespan of C. elegans by reducing reactive oxygen species levels, a finding corroborated by Xu et al.(2023) who reported significant improvements in C. elegans survival with curcumin treatment. These findings may help explain why curcumin did not exhibit lethal effects on larvae of the organisms studied here. Interestingly, although curcumin promotes positive effects in this model nematode, several studies highlight its promising anthelminthic potential parasites such as Schistosoma mansoni (Abu Almaaty et al. 2021 ; Badoco et al. 2022 ; de Paula Aguiar et al. 2016 ; Luz et al. 2012 ; Magalhães et al. 2009 ), Fasciola gigantica (Rehman et al. 2020 ; Ullah et al. 2017 ), and Ascaridia galli (Bazh & El-Bahy 2013 ), likely through the induction of oxidative stress. These results suggest that curcumin’s mechanism of action may vary depending on the target organism. Despite the lack of activity by curcumin ( 1) , three analogs demonstrated substantial effects on C. elegans L3/L4 larval survival. Among them, curcuminoid 3 , which lacks substituent radicals on the aryl group compared to the curcumin structure, emerged as the most potent, exhibiting complete lethality against C. elegans L3/L4 larvae, with an EC 50 value < 6.25 µM. This analog also showed moderate nematicidal activity against M. exigua J2 larvae, with an EC 50 at 72h of approximately 57 µM. The use of natural products in drug discovery is an environmentally sustainable approach that supports the development of potent green pesticides (Wang et al., 2023 ). Notably, studies by Nunes et al. ( 2013 ) and Yadav et al. ( 2022 ) demonstrated that chalcones ( α , β -unsaturated ketone) significantly reduced M. incognita populations in vitro, a nematicidal effect similary observed by Caboni et al. ( 2016 ) These fundings support the nematicidal potential of compound 3 , which contains two α , β -unsaturated carbonyl groups linked by a β -ketone moiety, a structural characteristic associated with nematicidal activity. Curcuminoids 19 and 20 were also effective, inducing paralysis in 75% and 55% of C. elegans L3/L4 larvae, respectively. While curcumin exhibits a broad spectrum of biological activities, its chemical instability, low absorption, and rapid metabolism limit its effectiveness, prompting the development of curcumin analogs to enhance stability and bioavailability (Vieira et al. 2018 ). Indeed, the extensive documentation of the biological properties of these curcuminoids (Vieira et al. 2024 ) supports the superior efficacy observed in these analogs. The M. exigua J2 larvae represent the infective stage of this parasitic nematode, hatching from eggs and penetrating plant roots to migrate through the vascular system, where they initiate feeding and undergo three additional developmental stages before reaching adulthood. Each adult female can lay approximately 250 eggs, from which new J2 larvae hatch, perpetuating the life cycle (Atamian et al. 2012 ). Egg hatch assays are highly recommended in vitro methods for detecting resistance in nematodes (Calvete et al. 2014 ), and for assessing the ovicidal potential of new pesticides, thereby interrupting the parasite’s life cycle (Easland et al. 2023 ). Following 24-hour incubation with curcuminoids, C. elegans egg hatching was completely inhibited at concentrations ranging 100 µM to 12.5 µM of analog 3 and was significantly reduced by compounds 19 and 20 , with egg hatching decreasing by 84–68%, respectively. Additionally, all these three curcuminoids effectively inhibited 100% of M. exigua egg hatching. Notably, curcumin A ( 2 ), which was inactive in nematicidal assays, inhibited 100% of M. exigua egg hatching across all evaluated concentrations (100 µM to 6.25 µM). These findings underscore the ovicidal potential of curcumin analogs in both C. elegans and M. exigua models. Multiple studies have reported the ovicidal properties of plant-derived compounds. For example, Rosmarinus officinalis (Pinto et al. 2019 ), Brongniartia montalvoana (Cortes-Morales et al. 2022 ), and various saponins and flavonoids (Santos et al. 2018 ) exhibit larvicidal and ovicidal effects against nematodes infections in small ruminants. These findings collectively support the application of plant-derived molecules in drug discovery as promising sources of new ovicidal agents. Although the precise mechanism of action of these curcuminoids remains unclear, we were able to confirm their efficacy against the larvae and eggs of two nematode species. According to Integrated Pest Management (IPM) principles, key strategies for sustainable pest control include the use of low-toxicity pesticides, precise application, and selecting products with minimal environmental persistence (Falkenberg et al. 2022 ). In this context, curcumin analogs contribute to advancing scientific knowledge toward innovative, sustainable solutions for managing plant-parasites nematodes, such as Meloidogyne spp. The findings from this study highlight these analogs as promising nematicidal candidates, with activity comparable to fluensulfone, the standard pesticide for Meloidogyne spp. This research highlights the nematicidal potential of curcuminoids, particularly curcuminoid 3 , against the plant-parasitic nematode M. exigua . Curcuminoid 3 demonstrated strong efficacy by paralyzing L3/L4 larvae and adults C. elegans and inhibits egg hatching, while also significantly affecting J2 larvae and egg hatching in M. exigua , this study confirms curcuminoid activity across various nematode developmental stages. These findings support the development of sustainable, eco-friendly strategies for managing plant-parasitic nematodes in coffee plantations and suggest promising avenues for future agricultural applications to aimed at mitigating the impact of these pests on coffee crops. Declarations Conflict of interest Authors have declared that no competing interests exist. Author contributions Lucas S. M. U. Lima, and Lucas A. de L. Paula performed the biological assays, analyzed the data, and wrote the manuscript. Matheus H. M. Zago helped with the biological assays. Tatiana M. Vieira, and Antônio E. M. Crotti synthesized the curcumin analogs. Alessandra M. Vacari, and Lizandra G. 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Reactions of reactive oxygen species (ROS) with curcumin analogues: Structure–activity relationship. Free Radical Research, 45(3), 317–325. https://doi.org/10.3109/10715762.2010.532493 Souza JM, Vieira TM, Candido ACBB, Tezuka DY, Rao GS, de Albuquerque S, Crotti AEM, Siqueira-Neto JL, Magalhães LG (2021). In vitro anti- Trypanosoma cruzi activity enhancement of curcumin by its monoketone tetramethoxy analog diveratralacetone. Current Research in Parasitology & Vector-Borne Diseases, 1, 100031. https://doi.org/10.1016/j.crpvbd.2021.100031 Stiernagle T (2006). Maintenance of C. elegans . In WormBook: the online review of C. elegans biology (pp. 1–11). https://doi.org/10.1895/wormbook.1.101.1 Tapia-Vázquez I, Montoya-Martínez A C, De los Santos-Villalobos S, Ek-Ramos MJ, Montesinos-Matías R, Martínez-Anaya C (2022). Root-knot nematodes ( Meloidogyne spp.) a threat to agriculture in Mexico: biology, current control strategies, and perspectives. World Journal of Microbiology and Biotechnology, 38(2), 26. https://doi.org/10.1007/s11274-021-03211-2 Thi Phan N, Besnard G, Ouazahrou R, Sánchez WS, Gil L, Manzi S, Bellafiore S (2021). Genome sequence of the coffee root-knot nematode Meloidogyne exigua . Journal of Nematology, 53(1), 1–6. https://doi.org/10.21307/jofnem-2021-065 Ullah R, Rehman A, Zafeer MF, Rehman L, Khan YA, Khan MAH, Khan SN, Khan AU, Abidi SMA (2017). Anthelmintic Potential of Thymoquinone and Curcumin on Fasciola gigantica . PLOS ONE, 12(2), e0171267. https://doi.org/10.1371/journal.pone.0171267 Venzon M (2021). Agro-Ecological Management of Coffee Pests in Brazil. Frontiers in Sustainable Food Systems, 5. https://doi.org/10.3389/fsufs.2021.721117 Vieira TM, dos Santos IA, Silva TS, Martins CHG, Crotti AEM (2018). Antimicrobial activity of monoketone curcuminoids against cariogenic bacteria. 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Bioefficacy evaluation of ferrocenyl chalcones against Meloidogyne incognita and Sclerotium rolfsii infestation in tomato. Journal of Environmental Science and Health, Part B, 57(3), 192–200. https://doi.org/10.1080/03601234.2022.2042154 Zorofchian Moghadamtousi S, Abdul Kadir H, Hassandarvish P, Tajik H, Abubakar S, Zandi K (2014). A Review on Antibacterial, Antiviral, and Antifungal Activity of Curcumin. BioMed Research International, 2014 , 1–12. https://doi.org/10.1155/2014/186864 Table 1 Table 1 is available in the Supplementary Files section. Supplementary Files Table1.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7242730","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":497531441,"identity":"1a8ccd7b-6571-42f5-9ab7-559e26517551","order_by":0,"name":"Lucas S. M. 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Among the 130 recognized species in the \u003cem\u003eCoffea\u003c/em\u003e genus, \u003cem\u003eCoffea arabica\u003c/em\u003e L. (Arabica coffee) and \u003cem\u003eCoffea canephora\u003c/em\u003e Pierre ex A. Froehner (Robusta coffee) are the most extensively cultivated (Guyot et al. \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). In the first eight months of 2024, Brazil exported coffee to 138 countries, with the United States and Germany as the primary importers (Cecaf\u0026eacute; \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). As the world\u0026rsquo;s leading coffee producer and exporter, Brazil\u0026rsquo;s Arabica production is projected to reach 99.9\u0026nbsp;million 60-kg bags, accounting for 56.7% of global supply (Cecaf\u0026eacute; \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2025\u003c/span\u003e). Between January and September, Brazil set a record by exporting 36.428\u0026nbsp;million bags, generating US\u003cspan\u003e$\u003c/span\u003e 8.451\u0026nbsp;billion in revenue (Cecaf\u0026eacute; \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2025\u003c/span\u003e; Santana et al. \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). However, coffee production faces substantial challenges, including water scarcity and pest infestations\u0026mdash;particularly from plant-parasitic nematodes (root-knot nematodes), which can reduce global coffee yields by approximately 15% and impact Brazil\u0026rsquo;s production by up to 20% (Pinto \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; Venzon \u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e2021\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe root-knot nematodes (RKN) of the genus \u003cem\u003eMeloidogyne\u003c/em\u003e, particularly \u003cem\u003eM. exigua\u003c/em\u003e, \u003cem\u003eM. incognita\u003c/em\u003e, and \u003cem\u003eM. paranaenses\u003c/em\u003e, are highly detrimental to coffee cultivation in Brazil. These nematodes have a complex life cycle that begins with egg hatching, followed by larval migration to plant roots, where they induce gall formation (Carneiro \u0026amp; Cofcewicz \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2008\u003c/span\u003e; Santos et al. \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). These galls hinder water and nutrient absorption, weakening the plant and reducing productivity (Afridi et al. \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). Nematode spread can occur via infected seedlings, runoff, or contaminated agricultural equipment, underscoring the importance of preventive management strategies (Lamelas et al. \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Matiello et al. \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; M. F. A. Santos et al. \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). On the other hand, \u003cem\u003eCaenorhabditis elegans\u003c/em\u003e\u0026mdash;a free-living nematode frequently used as a model organism in biological research\u0026mdash;is maintained easily in laboratory settings and shares key biological traits with plant-parasitic nematodes like \u003cem\u003eMeloidogyne\u003c/em\u003e (Corsi et al. \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2018\u003c/span\u003e; Cortese et al. \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2006\u003c/span\u003e). These similarities, which include conserved metabolic pathways and sensory neuroanatomy, allow \u003cem\u003eC. elegans\u003c/em\u003e to serve as a model for studying parasitic nematodes (Rengarajan \u0026amp; Hallem \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e2016\u003c/span\u003e; Shivakumara et al. \u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e2019\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eControl methods for plant-parasitic nematodes include preventive practices, such as utilizing healthy seedlings and implementing conservation agriculture techniques, alongside chemical and biological nematicides (Matiello et al. \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). The most widely used chemical nematicides are organophosphates and carbamates. However, the development of new nematicides has been limited, with few products introduced to the market since 1970s(Cao et al. \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2022\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eCertain plants, particularly those of the genus \u003cem\u003eCurcuma\u003c/em\u003e, are recognized for their resistance to nematodes and other pests. Curcumin, a key compound in \u003cem\u003eCurcuma longa\u003c/em\u003e, (Kocaadam \u0026amp; Şanlier 2017; Kotha \u0026amp; Luthria \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e2019\u003c/span\u003e) has demonstrated notable biological activities, including nematicidal effects. However, its application is limited due to its low bioavailability and rapid degradation (Anand et al. \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2007\u003c/span\u003e; Singh et al. \u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e2011\u003c/span\u003e). Synthetic analogs of curcumin, modified in the central carbon chain, offer improved stability and enhanced antiparasitic activity (Carapina da Silva et al. \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; Chauhan et al. \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2018\u003c/span\u003e; Rai et al. \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Souza et al. \u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Vieira et al. \u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; Zorofchian Moghadamtousi et al. \u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e2014\u003c/span\u003e). Although curcumin\u0026rsquo;s efficacy has been documented against \u003cem\u003eAscaridia galli\u003c/em\u003e, its effects on RKN, specifically within the genus of the genus \u003cem\u003eMeloidogyne\u003c/em\u003e, remain unreported (Bazh \u0026amp; El-Bahy \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2013\u003c/span\u003e). This study aims to evaluate the nematicide effects of curcumin (\u003cb\u003e1\u003c/b\u003e) and a range of synthetic monoketone curcuminoid analogs (\u003cb\u003e2\u0026ndash;23\u003c/b\u003e) on \u003cem\u003eC. elegans\u003c/em\u003e and \u003cem\u003eM. exigua in vitro\u003c/em\u003e.\u003c/p\u003e"},{"header":"Material and methods","content":"\u003cp\u003e\u003cb\u003eDrugs\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe synthesis methods of all test compounds (\u003cb\u003e2\u0026ndash;23\u003c/b\u003e) have been previously described in the literature (Vieira et al. \u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). Levamisole, used as a positive control for the \u003cem\u003eC. elegans\u003c/em\u003e assays, and curcumin (\u003cb\u003e1\u003c/b\u003e) were obtained from Sigma-Aldrich (St. Louis, MO, USA). For the \u003cem\u003eM. exigua\u003c/em\u003e assays, fluensulfone (Nimitz\u0026reg;, ADAMA, Asdode, Israel) served as the positive control. All tested compounds had a purity of at least 95%, except curcumin, which was 80% pure.\u003c/p\u003e\u003cp\u003e\u003cb\u003eNematodes cultures\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe wild-type \u003cem\u003eC. elegans\u003c/em\u003e strain (Bristol N2) was maintained on nematode growth medium (NGM) agar plates inoculated with \u003cem\u003eEscherichia coli\u003c/em\u003e OP50 at 20\u0026deg;C, following established according to standard protocols (Stiernagle \u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e2006\u003c/span\u003e). Synchronous populations were prepared for all experiments using a standard bleaching method (Stiernagle \u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e2006\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cem\u003eMeloidogyne exigua\u003c/em\u003e population used in the experiments was obtained from coffee plants in Ribeir\u0026atilde;o Corrente, SP, Brazil (20\u0026deg;32\u0026rsquo;30\u0026rsquo;\u0026rsquo; S and 47\u0026deg;25\u0026rsquo;11\u0026rsquo;\u0026rsquo; W), and identified by α-esterase phenotypes (Carneiro \u0026amp; Cofcewicz \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2008\u003c/span\u003e). This population was maintained on \u003cem\u003eCoffea arabica\u003c/em\u003e \u0026lsquo;Mundo Novo\u0026rsquo; under greenhouse conditions. Approximately 4 days prior the bioassays, eggs and J2 juveniles were extracted from soil and roots following the Boneti and Ferraz method (1981). The extracted nematodes were quantified using a Peters\u0026rsquo; slide and subsequently used as inoculum.\u003c/p\u003e\u003cp\u003e\u003cb\u003eScreening of compounds against\u003c/b\u003e \u003cb\u003eC. elegans\u003c/b\u003e \u003cb\u003eat L3/L4 and adult stages of, and EC\u003c/b\u003e\u003csub\u003e\u003cb\u003e50\u003c/b\u003e\u003c/sub\u003e \u003cb\u003edetermination\u003c/b\u003e\u003c/p\u003e\u003cp\u003eFor the screening of compounds against \u003cem\u003eC. elegans\u003c/em\u003e, 10 worms at the L3/L4 stage were placed into each well of a 96-well plate containing 150 \u0026micro;L of S medium.\u003csup\u003e31\u003c/sup\u003e Compounds \u003cb\u003e1\u003c/b\u003e\u0026ndash;\u003cb\u003e23\u003c/b\u003e, previously dissolved in dimethyl sulfoxide (DMSO) (Sigma-Aldrich), were added at a concentration of 50 \u0026micro;M. The nematodes were incubated at 20\u0026deg;C for 24 h, and motility changes were assessed visually using a Zeiss Axiovert 40 C inverted microscope (Zeiss). All nematodes were categorized as either mobile or immobile (paralyzed, defined as showing no movement for 1 minute of observation) (Luo et al. \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). Control groups included nematodes in S medium with 0.1% DMSO (the negative control) and a positive control group treated with levamisole (Sigma-Aldrich) at 24 \u0026micro;M. Each experiment was conducted in duplicate and repeated twice for consistency.\u003c/p\u003e\u003cp\u003eTo determining the 50% effective concentration (EC\u003csub\u003e50\u003c/sub\u003e), experiments were conducted as previously above with the compounds that caused paralysis in more than 50% of the nematodes in the screening, and evaluated at concentrations ranging from 6.25 to 100 \u0026micro;M, while levamisole was evaluated at concentrations from 6.25 to 50 \u0026micro;M.\u003c/p\u003e\u003cp\u003e\u003cb\u003eIn vitro\u003c/b\u003e \u003cb\u003enematocidal assay against\u003c/b\u003e \u003cb\u003eM. exigua\u003c/b\u003e \u003cb\u003eJ2 larvae\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe nematicide activity of compounds \u003cb\u003e1\u003c/b\u003e, \u003cb\u003e2\u003c/b\u003e, \u003cb\u003e3\u003c/b\u003e, \u003cb\u003e19\u003c/b\u003e, and \u003cb\u003e20\u003c/b\u003e was evaluated against \u003cem\u003eM. exigua\u003c/em\u003e J2 larvae following the protocol by Silva et al. (\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). The compounds were dissolved in DMSO and tested at concentrations ranging from 6.25 to 100 \u0026micro;M, while fluensulfone (Nimitz\u0026reg;) was tested at final concentrations ranging from 3.75 to 60 \u0026micro;g.mL\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e (equivalent to 12.85 to 205 \u0026micro;M) (Pacule \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). Approximately 10 J2 larvae were placed in each well of a 24-well plate along with the compounds and incubated in the dark at 28\u0026deg;C for 72 h. After this period, the solution was replaced with mineral water for an additional 24 h to confirm mortality by observing immobility. J2 larvae that remained immobile, straightened, or exhibited abnormal morphology were classified as dead (Franzener et al., \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2007\u003c/span\u003e). Control groups, nematodes were incubated in mineral water containing 0.1% DMSO (negative control) or fluensulfone (Nimitz\u0026reg;) at 62.2 \u0026micro;g.mL\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e (positive control).\u003c/p\u003e\u003cp\u003e\u003cb\u003eEvaluation of egg hatching for\u003c/b\u003e \u003cb\u003eC. elegans\u003c/b\u003e \u003cb\u003eand\u003c/b\u003e \u003cb\u003eM. exigua\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe eggs from \u003cem\u003eC. elegans\u003c/em\u003e and \u003cem\u003eM. exigua\u003c/em\u003e were obtained following the protocols by Stiernagle (\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e2006\u003c/span\u003e), and Boneti \u0026amp; Ferraz (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e1981\u003c/span\u003e), respectively. Approximately 50 \u0026micro;L of an egg suspension (~\u0026thinsp;50 eggs) was added to each well of a 96-well plate, containing M9 buffer for \u003cem\u003eC. elegans\u003c/em\u003e or mineral water for \u003cem\u003eM. exigua\u003c/em\u003e. Compounds \u003cb\u003e1\u003c/b\u003e, \u003cb\u003e2\u003c/b\u003e, \u003cb\u003e3\u003c/b\u003e, \u003cb\u003e19\u003c/b\u003e, and \u003cb\u003e20\u003c/b\u003e, dissolved in DMSO, were tested at concentrations ranging from 6.25 to 100 \u0026micro;M. \u003cem\u003eC. elegans\u003c/em\u003e eggs were incubated at 20\u0026deg;C for 24 h, while \u003cem\u003eM. exigua\u003c/em\u003e eggs were kept at room temperature in the dark and observed for up to 10 days. Following incubation, L1 larvae counts were conducted visually using a Zeiss Axiovert 40 C inverted microscope. Control groups included eggs in M9 buffer with 0.1% DMSO (\u003cem\u003eC. elegans\u003c/em\u003e) or in mineral water with 0.1% DMSO (\u003cem\u003eM. exigua\u003c/em\u003e). For \u003cem\u003eM. exigua\u003c/em\u003e, fluensulfone (Nimitz\u0026reg;) at 62.2 \u0026micro;g.mL\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e (213.23 \u0026micro;M) served as a positive control, while levamisole was excluded due to its lack of ovicidal activity (Albuquerque \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; Pacule \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e2020\u003c/span\u003e).\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eResults were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) of three independent experiments conducted in triplicate and converted to percentage values. Experimental data were analyzed for normality using the Shapiro-Wilk test, followed by one-way analysis of variance (ANOVA) with significance assessed by the Dunnett test. EC\u003csub\u003e50\u003c/sub\u003e values were determined from the dose-response inhibition curve using nonlinear regression, with 95% confidence intervals calculated for each EC\u003csub\u003e50\u003c/sub\u003e value. All statistical analyses were performed using GraphPad Prism version 8.0 for Windows (GraphPad Software, USA).\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eCurcuminoid 3 exhibits nematicidal activity against\u003c/strong\u003e \u003cstrong\u003eC. elegans\u003c/strong\u003e \u003cstrong\u003eL3/L4 larvae\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAn initial screening was conducted with curcumin (\u003cstrong\u003e1\u003c/strong\u003e) and the synthetic monoketone curcuminoid analogs (2\u0026ndash;22) at 50 \u0026micro;M for 24 h against \u003cem\u003eC. elegans\u003c/em\u003e L3/L4 larvae. As showed in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, curcumin (\u003cstrong\u003e1\u003c/strong\u003e) and curcumin A (\u003cstrong\u003e2\u003c/strong\u003e), a more stable analog, did not exhibit any nematicide effect. In contrast, analog 3 emerged as the most potent compound, resulting in 100% larval mortality after the incubation period. Compounds \u003cstrong\u003e4\u003c/strong\u003e and \u003cstrong\u003e5\u003c/strong\u003e were inactive during screening. Besides compound \u003cstrong\u003e3\u003c/strong\u003e, analog \u003cstrong\u003e19\u003c/strong\u003e also showed significant activity, paralyzing 75% of the larvae, while compound \u003cstrong\u003e20\u003c/strong\u003e demonstrated moderate efficacy with 55% motor unresponsiveness (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Levamisole, used as a positive control at 24 \u0026micro;M, caused complete larval lethality. Based on these findings, curcuminoids \u003cstrong\u003e3\u003c/strong\u003e, \u003cstrong\u003e19\u003c/strong\u003e, and \u003cstrong\u003e20\u003c/strong\u003e were selected for further evaluation to determine their EC\u003csub\u003e50\u003c/sub\u003e values over a concentration range of 6.25 to 100 \u0026micro;M (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). Curcumin (\u003cstrong\u003e1\u003c/strong\u003e) and curcumin A (\u003cstrong\u003e2\u003c/strong\u003e) were also included in this assessment for structural comparation with monoketone analogs.\u003c/p\u003e\n\u003cp\u003eTable \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003eAfter 24 h of exposure to curcumin (\u003cstrong\u003e1\u003c/strong\u003e), curcumin A (\u003cstrong\u003e2\u003c/strong\u003e), and the analogs \u003cstrong\u003e3\u003c/strong\u003e, \u003cstrong\u003e19\u003c/strong\u003e, and \u003cstrong\u003e20\u003c/strong\u003e, compound \u003cstrong\u003e3\u003c/strong\u003e demonstrated strong nematicidal potential, achieving an EC\u003csub\u003e50\u003c/sub\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;6.25 \u0026micro;M for both \u003cem\u003eC. elegans\u003c/em\u003e L3/L4 and adult stages (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). This potency exceeded that of the positive control, levamisole, which presented an EC\u003csub\u003e50\u003c/sub\u003e of 10.50 \u0026micro;M (3.45\u0026ndash;26.04 \u0026micro;M) for the L3/L4 stage and 14.99 \u0026micro;M (7.22\u0026ndash;29.53 \u0026micro;M) adult worms. Curcumin (\u003cstrong\u003e1\u003c/strong\u003e) and curcumin A (\u003cstrong\u003e2\u003c/strong\u003e) showed no nematicidal activity at the tested concentrations. Regarding to compounds \u003cstrong\u003e19\u003c/strong\u003e and \u003cstrong\u003e20\u003c/strong\u003e exhibited promising nematicidal activity, with an EC\u003csub\u003e50\u003c/sub\u003e of approximately 33 \u0026micro;M for both L3/L4 and adult \u003cem\u003eC. elegans\u003c/em\u003e (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003ctable border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 2\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eDetermination of the effective concentration 50 (EC50) against Caernohabditis elegans and Meloidogyne exigua following incubation with curcumin and its synthetic monoketone curcuminoid analogs\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003eEC\u003csub\u003e50\u003c/sub\u003e\u003csup\u003ea\u003c/sup\u003e (\u0026micro;M)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eCompounds\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eC. elegans\u003c/em\u003e L3/L4 larvae (24 h)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eC. elegans\u003c/em\u003e adult (24 h)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eM. exigua\u003c/em\u003e J2\u003c/p\u003e\n \u003cp\u003e(24 h)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eM. exigua\u003c/em\u003e J2\u003c/p\u003e\n \u003cp\u003e(72 h)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;6.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;6.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e93.05\u003c/p\u003e\n \u003cp\u003e(79.87\u0026ndash;114.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e57.62\u003c/p\u003e\n \u003cp\u003e(50.56\u0026ndash;66.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e19\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50.82\u003c/p\u003e\n \u003cp\u003e(31.94\u0026ndash;105.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36.76\u003c/p\u003e\n \u003cp\u003e(17.77\u0026ndash;42.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e97.69\u003c/p\u003e\n \u003cp\u003e(81.78\u0026ndash;117.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e20\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33.76\u003c/p\u003e\n \u003cp\u003e(24.87\u0026ndash;41.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34.81\u003c/p\u003e\n \u003cp\u003e(27.94\u0026ndash;43.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e97.62\u003c/p\u003e\n \u003cp\u003e(81.43\u0026ndash;116.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e91.65\u003c/p\u003e\n \u003cp\u003e(77.67-111.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePositive control\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003eb\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.50\u003c/p\u003e\n \u003cp\u003e(3.45\u0026ndash;26.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.99\u003c/p\u003e\n \u003cp\u003e(7.22\u0026ndash;29.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e117.58\u003c/p\u003e\n \u003cp\u003e(96.65\u0026ndash;137.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e92.58\u003c/p\u003e\n \u003cp\u003e(78.01-113.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"5\"\u003e\n \u003cp\u003e\u003csup\u003ea\u003c/sup\u003eEC\u003csub\u003e50\u003c/sub\u003e: effective concentration required to paralyse 50% of the worms. \u003csup\u003eb\u003c/sup\u003ePositive control: levamisole (24 \u0026micro;M) for \u003cem\u003eC. elegans\u003c/em\u003e and fluensulfone (Nimitz\u0026reg;) (12.85 a 205 \u0026micro;M) for \u003cem\u003eM. exigua\u003c/em\u003e. Values in parentheses represent the 95% confidence interval.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCurcuminoid analogs exhibit moderate nematicidal activity against J2\u003c/strong\u003e \u003cstrong\u003eM. exigua\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe concentrations required for nematicide activity against J2 \u003cem\u003eM. exigua\u003c/em\u003e were consistently higher than those needed for \u003cem\u003eC. elegans\u003c/em\u003e at all time points (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). After 24 h and 72 h of incubation, curcumin (\u003cstrong\u003e1\u003c/strong\u003e), curcumin A (\u003cstrong\u003e2\u003c/strong\u003e), evaluated for structural comparation, exhibited an EC\u003csub\u003e50\u003c/sub\u003e values higher than100 \u0026micro;M. In contrast, the curcuminoid analogs \u003cstrong\u003e19\u003c/strong\u003e and \u003cstrong\u003e20\u003c/strong\u003e displayed EC\u003csub\u003e50\u003c/sub\u003e values equal to or exceeding 91 \u0026micro;M. Compound \u003cstrong\u003e3\u003c/strong\u003e demonstrated moderate efficacy against J2 larvae after 24 and 72 h exposure, with EC\u003csub\u003e50\u003c/sub\u003e values of 93.05 \u0026micro;M (79.87\u0026ndash;114.0 \u0026micro;M) and 57.62 \u0026micro;M (50.56\u0026ndash;66.47 \u0026micro;M), respectively. For the positive control, fluensulfone ((Nimitz\u0026reg;), the EC\u003csub\u003e50\u003c/sub\u003e values were found were to be \u0026gt;\u0026thinsp;100 \u0026micro;M and 92.58 \u0026micro;M (78.01-113.56) for 24 h and 72 h, respectively.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCurcuminoid analogs inhibit egg hatching in\u003c/strong\u003e \u003cstrong\u003eC. elegans\u003c/strong\u003e \u003cstrong\u003eand\u003c/strong\u003e \u003cstrong\u003eM. exigua.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe use of ovicidal assays in anthelminthic drug discovery represents a promising strategy for disrupting the life cycle of parasitic worms by preventing egg hatching (Easland et al. \u003cspan class=\"CitationRef\"\u003e2023\u003c/span\u003e; Sch\u0026auml;rer et al. \u003cspan class=\"CitationRef\"\u003e2023\u003c/span\u003e). To evaluated the ovicidal potential of compounds, eggs from \u003cem\u003eC. elegans\u003c/em\u003e and \u003cem\u003eM. exigua\u003c/em\u003e were incubated with various concentrations of the compounds and assessed for hatching after 24 h or monitored over a 10-day period, respectively. As shown in Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e, compounds \u003cstrong\u003e1\u003c/strong\u003e and \u003cstrong\u003e2\u003c/strong\u003e didn\u0026rsquo;t exhibit any effect on the eggs of \u003cem\u003eC. elegans\u003c/em\u003e. In line with the nematicidal assays, curcuminoid \u003cstrong\u003e3\u003c/strong\u003e completely inhibited egg hatching in \u003cem\u003eC. elegans\u003c/em\u003e at concentrations ranging from 100 \u0026micro;M to 12.5 \u0026micro;M, with a significant reduction in hatching observed at 6.25 \u0026micro;M. Compounds \u003cstrong\u003e19\u003c/strong\u003e and \u003cstrong\u003e20\u003c/strong\u003e also demonstrated significant reductions in egg hatching for \u003cem\u003eC. elegans\u003c/em\u003e, with 23.00\u0026thinsp;\u0026plusmn;\u0026thinsp;2.64%, and 34.00\u0026thinsp;\u0026plusmn;\u0026thinsp;4.00% of eggs hatching at 100 \u0026micro;M and 50 \u0026micro;M, respectively. Additionally, \u003cstrong\u003e20\u003c/strong\u003e exhibited 43.67\u0026thinsp;\u0026plusmn;\u0026thinsp;4.72% and 46.33\u0026thinsp;\u0026plusmn;\u0026thinsp;5.85% hatching rates at these concentrations. It is noteworthy that levamisole, the nematicide drug used for \u003cem\u003eC. elegans\u003c/em\u003e, does not exhibit any ovicidal effect on the eggs of the worm.\u003c/p\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eEvaluation of Caernohabditis elegans and Meloidogyne exiguas egg hatching after exposure to curcumin and synthetic monoketone curcuminoid analogs\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" style=\"width: 5.5186%;\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"7\" style=\"width: 31.1275%;\"\u003e\n \u003cp\u003e% Hatched eggs\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 5.5186%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.309%;\"\u003e\n \u003cp\u003e6.25 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.2391%;\"\u003e\n \u003cp\u003e12.5 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.2391%;\"\u003e\n \u003cp\u003e25 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6803%;\"\u003e\n \u003cp\u003e50 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6803%;\"\u003e\n \u003cp\u003e100 \u0026micro;M\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.2391%;\"\u003e\n \u003cp\u003eC-\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.1913%;\"\u003e\n \u003cp\u003eC\u0026thinsp;+\u0026thinsp;\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 5.5186%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eC. elegans\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003ec\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.309%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.2391%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.2391%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6803%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6803%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.2391%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.1913%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 5.5186%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.309%;\"\u003e\n \u003cp\u003e85.00\u0026thinsp;\u0026plusmn;\u0026thinsp;13.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.2391%;\"\u003e\n \u003cp\u003e86.67\u0026thinsp;\u0026plusmn;\u0026thinsp;11.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.2391%;\"\u003e\n \u003cp\u003e88.00\u0026thinsp;\u0026plusmn;\u0026thinsp;8.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6803%;\"\u003e\n \u003cp\u003e89.33\u0026thinsp;\u0026plusmn;\u0026thinsp;6.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6803%;\"\u003e\n \u003cp\u003e84.00\u0026thinsp;\u0026plusmn;\u0026thinsp;7.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"5\" style=\"width: 5.2391%;\"\u003e\n \u003cp\u003e100.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.1913%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 5.5186%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.309%;\"\u003e\n \u003cp\u003e93.00\u0026thinsp;\u0026plusmn;\u0026thinsp;5.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.2391%;\"\u003e\n \u003cp\u003e90.00\u0026thinsp;\u0026plusmn;\u0026thinsp;10.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.2391%;\"\u003e\n \u003cp\u003e88.00\u0026thinsp;\u0026plusmn;\u0026thinsp;8.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6803%;\"\u003e\n \u003cp\u003e90.00\u0026thinsp;\u0026plusmn;\u0026thinsp;6.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6803%;\"\u003e\n \u003cp\u003e87.67\u0026thinsp;\u0026plusmn;\u0026thinsp;9.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.1913%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 5.5186%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.309%;\"\u003e\n \u003cp\u003e21.67\u0026thinsp;\u0026plusmn;\u0026thinsp;2.88\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.2391%;\"\u003e\n \u003cp\u003e0.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.57\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.2391%;\"\u003e\n \u003cp\u003e0.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.57\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6803%;\"\u003e\n \u003cp\u003e0.66\u0026thinsp;\u0026plusmn;\u0026thinsp;1.15\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6803%;\"\u003e\n \u003cp\u003e0.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.00\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.1913%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 5.5186%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e19\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.309%;\"\u003e\n \u003cp\u003e92.67\u0026thinsp;\u0026plusmn;\u0026thinsp;3.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.2391%;\"\u003e\n \u003cp\u003e75.67\u0026thinsp;\u0026plusmn;\u0026thinsp;5.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.2391%;\"\u003e\n \u003cp\u003e62.33\u0026thinsp;\u0026plusmn;\u0026thinsp;3.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6803%;\"\u003e\n \u003cp\u003e43.67\u0026thinsp;\u0026plusmn;\u0026thinsp;4.72\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6803%;\"\u003e\n \u003cp\u003e23.00\u0026thinsp;\u0026plusmn;\u0026thinsp;2.64\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.1913%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 5.5186%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e20\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.309%;\"\u003e\n \u003cp\u003e100.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.2391%;\"\u003e\n \u003cp\u003e100.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.2391%;\"\u003e\n \u003cp\u003e100.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6803%;\"\u003e\n \u003cp\u003e46.33\u0026thinsp;\u0026plusmn;\u0026thinsp;5.85\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6803%;\"\u003e\n \u003cp\u003e34.00\u0026thinsp;\u0026plusmn;\u0026thinsp;4.00\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.1913%;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 5.5186%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eM. exigua\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003ed\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.309%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.2391%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.2391%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6803%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6803%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.2391%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.1913%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 5.5186%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.309%;\"\u003e\n \u003cp\u003e90. 00\u0026thinsp;\u0026plusmn;\u0026thinsp;11.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.2391%;\"\u003e\n \u003cp\u003e85.00\u0026thinsp;\u0026plusmn;\u0026thinsp;10.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.2391%;\"\u003e\n \u003cp\u003e88. 00\u0026thinsp;\u0026plusmn;\u0026thinsp;9.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6803%;\"\u003e\n \u003cp\u003e76.70\u0026thinsp;\u0026plusmn;\u0026thinsp;6.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 4.6803%;\"\u003e\n \u003cp\u003e72.70\u0026thinsp;\u0026plusmn;\u0026thinsp;8.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"5\" style=\"width: 5.2391%;\"\u003e\n \u003cp\u003e100.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"5\" style=\"width: 4.1913%;\"\u003e\n \u003cp\u003e0.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.00\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 5.5186%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"5\" style=\"width: 25.078%;\"\u003e\n \u003cp\u003e0.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.00\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 5.5186%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"5\" style=\"width: 25.078%;\"\u003e\n \u003cp\u003e0.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.00\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 5.5186%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e19\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"5\" style=\"width: 25.078%;\"\u003e\n \u003cp\u003e0.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.00\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 5.5186%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e20\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"5\" style=\"width: 25.078%;\"\u003e\n \u003cp\u003e0.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.00\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"8\" style=\"width: 40.7256%;\"\u003e\n \u003cp\u003e\u003csup\u003ea\u003c/sup\u003eC-: negative control; M9 buffer with 0.1% DMSO for \u003cem\u003eC. elegans\u003c/em\u003e and mineral water with 0.1% DMSO for \u003cem\u003eM. exigua\u003c/em\u003e. \u003csup\u003eb\u003c/sup\u003e C+: positive control; fluensulfone (Nimitz\u0026reg;) at 62.2 \u0026micro;g/mL (213.23 \u0026micro;M) for \u003cem\u003eM. exigua;\u003c/em\u003e Levamisole was not included as a positive control for \u003cem\u003eC. elegans\u003c/em\u003e due to its lack of ovicidal activity. \u003csup\u003ec\u003c/sup\u003eEggs incubated with compounds for 24 h. \u003csup\u003ed\u003c/sup\u003eEggs incubated with compounds for 10 days. Data expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD from three different experiments. * p\u0026thinsp;\u0026lt;\u0026thinsp;005 indicates statistically different difference from the negative control group. \u0026ldquo;\u0026ndash;\u0026ldquo; denote data not evaluated.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eTable\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003eIn \u003cem\u003eM. exigua\u003c/em\u003e, the monoketone curcuminoid analogs \u003cstrong\u003e2, 3, 19\u003c/strong\u003e, and \u003cstrong\u003e20\u003c/strong\u003e inhibited egg hatching by 100%, demonstrating strong ovicidal activity (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). For comparison, the positive control fluensulfone (Nimitz\u0026reg;) also inhibited 100% of egg hatching, but only at 213 \u0026micro;M-twice the highest concentration tested for the curcuminoid compounds.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eRKN of the genus \u003cem\u003eMeloidogyne\u003c/em\u003e are sedentary parasites that have evolved complex strategies to penetrate and migrate through plant roots. They utilize different feeding mechanisms, targeting either cortical or vascular cells to support their development and reproduction (Perrine-Walker \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). These adaptations place them among the most destructive agricultural pests, causing significant reductions in crop yields, with coffee being particularly impacted (Tapia-V\u0026aacute;zquez et al. \u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Thi Phan et al. \u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). Among \u003cem\u003eMeloidogyne\u003c/em\u003e species, \u003cem\u003eM. exigua\u003c/em\u003e is especially harmful to coffee production, predominantly in Central and South America, where it is the most prevalent nematode in coffee-growing regions. The economic impact of RKN is substantial, with global annual losses estimated to exceed USD 170\u0026nbsp;billion (Elling \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2013\u003c/span\u003e). Although nematode control typically includes various pest management strategies, such as short-term nematicide applications, many traditional nematicides have been banned in recent years due to environmental and health risks (Forghani \u0026amp; Hajihassani \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). Additionally, nematodes have developed resistance to these conventional treatments, underscoring the urgent need for new nematicides with minimal risks to human and the environment (Nguyen et al. \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Research on \u003cem\u003eMeloidogyne\u003c/em\u003e species has been greatly informed by the model organism \u003cem\u003eC. elegans\u003c/em\u003e, as these two organisms share substantial genomic similarities, indicating conserved developmental and biochemical pathways (Nguyen et al. \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). \u003cem\u003eC. elegans\u003c/em\u003e is frequently used in studies investigating nematicide due to its small size, well-characterized genome, ease of maintenance, short life cycle, and efficient reproduction (Fuentes et al. \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Tapia-V\u0026aacute;zquez et al. \u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e2022\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIn this research, we investigated the nematicide and ovicidal effects of curcumin (\u003cb\u003e1\u003c/b\u003e) and a series of synthetic monoketone curcuminoid analogs against \u003cem\u003eC. elegans\u003c/em\u003e and \u003cem\u003eM. exigua\u003c/em\u003e. Curcumin (\u003cb\u003e1\u003c/b\u003e), the major compound of \u003cem\u003eCurcuma longa\u003c/em\u003e L. (turmeric), along with its structurally similar analog, curcumin A (\u003cb\u003e2\u003c/b\u003e), showed no nematicidal activity against either organism. Shen et al.(2013) demonstrated that curcumin (\u003cb\u003e1)\u003c/b\u003e could increase the mean lifespan of \u003cem\u003eC. elegans\u003c/em\u003e by reducing reactive oxygen species levels, a finding corroborated by Xu et al.(2023) who reported significant improvements in \u003cem\u003eC. elegans\u003c/em\u003e survival with curcumin treatment. These findings may help explain why curcumin did not exhibit lethal effects on larvae of the organisms studied here. Interestingly, although curcumin promotes positive effects in this model nematode, several studies highlight its promising anthelminthic potential parasites such as \u003cem\u003eSchistosoma mansoni\u003c/em\u003e (Abu Almaaty et al. \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Badoco et al. \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; de Paula Aguiar et al. \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2016\u003c/span\u003e; Luz et al. \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e2012\u003c/span\u003e; Magalh\u0026atilde;es et al. \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2009\u003c/span\u003e), \u003cem\u003eFasciola gigantica\u003c/em\u003e (Rehman et al. \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Ullah et al. \u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e2017\u003c/span\u003e), and \u003cem\u003eAscaridia galli\u003c/em\u003e (Bazh \u0026amp; El-Bahy \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2013\u003c/span\u003e), likely through the induction of oxidative stress. These results suggest that curcumin\u0026rsquo;s mechanism of action may vary depending on the target organism.\u003c/p\u003e\u003cp\u003eDespite the lack of activity by curcumin (\u003cb\u003e1)\u003c/b\u003e, three analogs demonstrated substantial effects on \u003cem\u003eC. elegans\u003c/em\u003e L3/L4 larval survival. Among them, curcuminoid \u003cb\u003e3\u003c/b\u003e, which lacks substituent radicals on the aryl group compared to the curcumin structure, emerged as the most potent, exhibiting complete lethality against \u003cem\u003eC. elegans\u003c/em\u003e L3/L4 larvae, with an EC\u003csub\u003e50\u003c/sub\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;6.25 \u0026micro;M. This analog also showed moderate nematicidal activity against \u003cem\u003eM. exigua\u003c/em\u003e J2 larvae, with an EC\u003csub\u003e50\u003c/sub\u003e at 72h of approximately 57 \u0026micro;M. The use of natural products in drug discovery is an environmentally sustainable approach that supports the development of potent green pesticides (Wang et al., \u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Notably, studies by Nunes et al. (\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e2013\u003c/span\u003e) and Yadav et al. (\u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e2022\u003c/span\u003e) demonstrated that chalcones (\u003cem\u003eα\u003c/em\u003e, \u003cem\u003eβ\u003c/em\u003e-unsaturated ketone) significantly reduced \u003cem\u003eM. incognita\u003c/em\u003e populations \u003cem\u003ein\u003c/em\u003e vitro, a nematicidal effect similary observed by Caboni et al. (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2016\u003c/span\u003e) These fundings support the nematicidal potential of compound \u003cb\u003e3\u003c/b\u003e, which contains two \u003cem\u003eα\u003c/em\u003e, \u003cem\u003eβ\u003c/em\u003e-unsaturated carbonyl groups linked by a \u003cem\u003eβ\u003c/em\u003e-ketone moiety, a structural characteristic associated with nematicidal activity.\u003c/p\u003e\u003cp\u003eCurcuminoids \u003cb\u003e19\u003c/b\u003e and \u003cb\u003e20\u003c/b\u003e were also effective, inducing paralysis in 75% and 55% of \u003cem\u003eC. elegans\u003c/em\u003e L3/L4 larvae, respectively. While curcumin exhibits a broad spectrum of biological activities, its chemical instability, low absorption, and rapid metabolism limit its effectiveness, prompting the development of curcumin analogs to enhance stability and bioavailability (Vieira et al. \u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). Indeed, the extensive documentation of the biological properties of these curcuminoids (Vieira et al. \u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e2024\u003c/span\u003e) supports the superior efficacy observed in these analogs.\u003c/p\u003e\u003cp\u003eThe \u003cem\u003eM. exigua\u003c/em\u003e J2 larvae represent the infective stage of this parasitic nematode, hatching from eggs and penetrating plant roots to migrate through the vascular system, where they initiate feeding and undergo three additional developmental stages before reaching adulthood. Each adult female can lay approximately 250 eggs, from which new J2 larvae hatch, perpetuating the life cycle (Atamian et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2012\u003c/span\u003e). Egg hatch assays are highly recommended in vitro methods for detecting resistance in nematodes (Calvete et al. \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2014\u003c/span\u003e), and for assessing the ovicidal potential of new pesticides, thereby interrupting the parasite\u0026rsquo;s life cycle (Easland et al. \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2023\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eFollowing 24-hour incubation with curcuminoids, \u003cem\u003eC. elegans\u003c/em\u003e egg hatching was completely inhibited at concentrations ranging 100 \u0026micro;M to 12.5 \u0026micro;M of analog \u003cb\u003e3\u003c/b\u003e and was significantly reduced by compounds \u003cb\u003e19\u003c/b\u003e and \u003cb\u003e20\u003c/b\u003e, with egg hatching decreasing by 84\u0026ndash;68%, respectively. Additionally, all these three curcuminoids effectively inhibited 100% of \u003cem\u003eM. exigua\u003c/em\u003e egg hatching. Notably, curcumin A (\u003cb\u003e2\u003c/b\u003e), which was inactive in nematicidal assays, inhibited 100% of \u003cem\u003eM. exigua\u003c/em\u003e egg hatching across all evaluated concentrations (100 \u0026micro;M to 6.25 \u0026micro;M). These findings underscore the ovicidal potential of curcumin analogs in both \u003cem\u003eC. elegans\u003c/em\u003e and \u003cem\u003eM. exigua\u003c/em\u003e models.\u003c/p\u003e\u003cp\u003eMultiple studies have reported the ovicidal properties of plant-derived compounds. For example, \u003cem\u003eRosmarinus officinalis\u003c/em\u003e (Pinto et al. \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e2019\u003c/span\u003e), \u003cem\u003eBrongniartia montalvoana\u003c/em\u003e (Cortes-Morales et al. \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2022\u003c/span\u003e), and various saponins and flavonoids (Santos et al. \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e2018\u003c/span\u003e) exhibit larvicidal and ovicidal effects against nematodes infections in small ruminants. These findings collectively support the application of plant-derived molecules in drug discovery as promising sources of new ovicidal agents.\u003c/p\u003e\u003cp\u003eAlthough the precise mechanism of action of these curcuminoids remains unclear, we were able to confirm their efficacy against the larvae and eggs of two nematode species. According to Integrated Pest Management (IPM) principles, key strategies for sustainable pest control include the use of low-toxicity pesticides, precise application, and selecting products with minimal environmental persistence (Falkenberg et al. \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). In this context, curcumin analogs contribute to advancing scientific knowledge toward innovative, sustainable solutions for managing plant-parasites nematodes, such as \u003cem\u003eMeloidogyne\u003c/em\u003e spp. The findings from this study highlight these analogs as promising nematicidal candidates, with activity comparable to fluensulfone, the standard pesticide for \u003cem\u003eMeloidogyne\u003c/em\u003e spp.\u003c/p\u003e\u003cp\u003eThis research highlights the nematicidal potential of curcuminoids, particularly curcuminoid \u003cb\u003e3\u003c/b\u003e, against the plant-parasitic nematode \u003cem\u003eM. exigua\u003c/em\u003e. Curcuminoid \u003cb\u003e3\u003c/b\u003e demonstrated strong efficacy by paralyzing L3/L4 larvae and adults \u003cem\u003eC. elegans\u003c/em\u003e and inhibits egg hatching, while also significantly affecting J2 larvae and egg hatching in \u003cem\u003eM. exigua\u003c/em\u003e, this study confirms curcuminoid activity across various nematode developmental stages. These findings support the development of sustainable, eco-friendly strategies for managing plant-parasitic nematodes in coffee plantations and suggest promising avenues for future agricultural applications to aimed at mitigating the impact of these pests on coffee crops.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of interest\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAuthors have declared that no competing interests exist.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLucas S. M. U. Lima, and Lucas A. de L. Paula performed the biological assays, analyzed the data, and wrote the manuscript. Matheus H. M. Zago helped with the biological assays. Tatiana M. Vieira, and Ant\u0026ocirc;nio E. M. Crotti synthesized the curcumin analogs. Alessandra M. Vacari, and Lizandra G. Magalh\u0026atilde;es designed the experiments, project administration and funding acquisition.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAckowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the National Council for Scientific and Technological Development, Brazil-CNPq (Fellowship: 303946/2018-0), Coordination for the Improvement of Higher Education Personnel, Brazil-CAPES (Finance code 001, Process number 88882.365793/2019-01) and S\u0026atilde;o Paulo Research Foundation, Brazil-FAPESP (2016/24456-1 and 2018/50011-2).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAbu Almaaty AH, Rashed HAE, Soliman MFM, Fayad E, Althobaiti F, El-Shenawy NS (2021). Parasitological and Biochemical Efficacy of the Active Ingredients of \u003cem\u003eAllium sativum\u003c/em\u003e and \u003cem\u003eCurcuma longa\u003c/em\u003e in \u003cem\u003eSchistosoma mansoni\u003c/em\u003e Infected Mice. 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Journal of Nematology, 53(1), 1\u0026ndash;6. https://doi.org/10.21307/jofnem-2021-065\u003c/li\u003e\n\u003cli\u003eUllah R, Rehman A, Zafeer MF, Rehman L, Khan YA, Khan MAH, Khan SN, Khan AU, Abidi SMA (2017). Anthelmintic Potential of Thymoquinone and Curcumin on \u003cem\u003eFasciola gigantica\u003c/em\u003e. PLOS ONE, 12(2), e0171267. https://doi.org/10.1371/journal.pone.0171267\u003c/li\u003e\n\u003cli\u003eVenzon M (2021). Agro-Ecological Management of Coffee Pests in Brazil. Frontiers in Sustainable Food Systems, 5. https://doi.org/10.3389/fsufs.2021.721117\u003c/li\u003e\n\u003cli\u003eVieira TM, dos Santos IA, Silva TS, Martins CHG, Crotti AEM (2018). Antimicrobial activity of monoketone curcuminoids against cariogenic bacteria. Chemistry \u0026amp; Biodiversity, 5\u0026ndash;12. https://doi.org/10.1002/cbdv.201800216\u003c/li\u003e\n\u003cli\u003eVieira TM, Tanajura LS, Heleno VCG, Magalh\u0026atilde;es LG, Crotti AEM (2024). Monoketone Curcuminoids: An Updated Review of Their Synthesis and Biological Activities. \u003cem\u003eFuture \u003c/em\u003ePharmacology, 4(1), 54\u0026ndash;77. https://doi.org/10.3390/futurepharmacol4010006\u003c/li\u003e\n\u003cli\u003eWang K, Wang B, Ma H, Wang Z, Liu Y, Wang Q (2023). Natural Products for Pesticides Discovery: Structural Diversity Derivation and Biological Activities of Naphthoquinones Plumbagin and Juglone. Molecules, 28(8), 3328. https://doi.org/10.3390/molecules28083328\u003c/li\u003e\n\u003cli\u003eXu J, Du P, Liu X, Xu X, Ge Y, Zhang C (2023). Curcumin supplementation increases longevity and antioxidant capacity in \u003cem\u003eCaenorhabditis elegans\u003c/em\u003e. Frontiers in Pharmacology, 14. https://doi.org/10.3389/fphar.2023.1195490\u003c/li\u003e\n\u003cli\u003eYadav DK, Kaushik P, Tripathi KP, Rana VS, Yeasin M, Kamil D, Pankaj KD, Shakil NA (2022). Bioefficacy evaluation of ferrocenyl chalcones against \u003cem\u003eMeloidogyne incognita\u003c/em\u003e and \u003cem\u003eSclerotium rolfsii\u003c/em\u003e infestation in tomato. Journal of Environmental Science and Health, Part B, 57(3), 192\u0026ndash;200. https://doi.org/10.1080/03601234.2022.2042154\u003c/li\u003e\n\u003cli\u003eZorofchian Moghadamtousi S, Abdul Kadir H, Hassandarvish P, Tajik H, Abubakar S, Zandi K (2014). A Review on Antibacterial, Antiviral, and Antifungal Activity of Curcumin. BioMed Research International, \u003cem\u003e2014\u003c/em\u003e, 1\u0026ndash;12. https://doi.org/10.1155/2014/186864\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table 1","content":"\u003cp\u003eTable 1 is available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Curcuminoids, Caenorhabditis elegans, Meloidogyne exigua, nematicide, ovicidal","lastPublishedDoi":"10.21203/rs.3.rs-7242730/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7242730/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eControl methods for plant-parasitic nematodes encompass preventive strategies, such as the use of healthy seedlings and the implementation of conservation agriculture practices, in addition to chemical and biological nematicides. The most widely used nematicides are organophosphates and carbamates. However, the development of new nematicides has been limited, with only a few products introduced to the market. This study aimed to assess \u003cem\u003ein vitro\u003c/em\u003e nematicidal properties of curcumin (\u003cb\u003e1\u003c/b\u003e) and a series synthetic monoketone curcuminoid analogs (\u003cb\u003e2\u0026ndash;23\u003c/b\u003e) against the model nematode \u003cem\u003eCaenorhabditis elegans\u003c/em\u003e and \u003cem\u003eMeloidogyne exigua\u003c/em\u003e, a significant pest in coffee plantations across Brazil. An initial screening at 50 \u0026micro;M revealed that curcumin (\u003cb\u003e1\u003c/b\u003e) and its more stable analog, curcumin A (\u003cb\u003e2\u003c/b\u003e), were ineffective. In contrast, curcuminoid \u003cb\u003e3\u003c/b\u003e induced 100% paralysis of \u003cem\u003eC. elegans\u003c/em\u003e L3/L4 larvae. Curcuminoids \u003cb\u003e19\u003c/b\u003e and \u003cb\u003e20\u003c/b\u003e exhibited partial activity, paralyzing 75% and 55% of the larvae, respectively. EC\u003csub\u003e50\u003c/sub\u003e assessments indicated that curcuminoid \u003cb\u003e3\u003c/b\u003e was highly potent against both L3/L4 larvae and adults of \u003cem\u003eC. elegans\u003c/em\u003e (EC\u003csub\u003e50\u003c/sub\u003e\u0026thinsp;\u0026lt;\u0026thinsp;6.25 \u0026micro;M). Notably, curcuminoid \u003cb\u003e3\u003c/b\u003e completely inhibited egg hatching. In tests against \u003cem\u003eM. exigua\u003c/em\u003e J2, curcuminoid \u003cb\u003e3\u003c/b\u003e displayed activity, whereas compounds 19 and 20 had an EC\u003csub\u003e50\u003c/sub\u003e\u0026thinsp;\u0026gt;\u0026thinsp;90 \u0026micro;M. All tested synthetic monoketone curcuminoid analogs successfully inhibited egg hatching. The results demonstrated the potential of synthetic monoketone curcuminoid analogs as promising nematicide agents, particularly in inhibiting egg hatching. These findings enhance our understanding of the biological effects of curcuminoids and open new avenues for developing effective strategies to control plant-parasitic nematodes, providing valuable tools for agricultural pest management.\u003c/p\u003e","manuscriptTitle":"Ovicidal and larvicidal properties of curcumin synthetic analogs against Caenorhabditis elegans and Meloidogyne exigua","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-13 10:38:32","doi":"10.21203/rs.3.rs-7242730/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a6501232-745d-40e1-906b-73a934561b98","owner":[],"postedDate":"August 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-10-06T06:35:08+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-13 10:38:32","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7242730","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7242730","identity":"rs-7242730","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}