Insecticidal activity of isoborneol derivatives against Musca domestica adults  and Culex quinquefasciatus larvae

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BHAT, Manisha O. Gupta, Roman Pavela, Chitra R. Kamath This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3839460/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 23 Aug, 2024 Read the published version in Environmental Science and Pollution Research → Version 1 posted 6 You are reading this latest preprint version Abstract Musca domestica L. , a common housefly, and Culex quinquefasciatus mosquito are quite well-known pests that can transfer a wide range of diseases to humans as well as animals. In this study, various isoborneol derivatives including esters, ethers and thioethers were synthesized fromisoborneol under mild conditions. These derivatives were evaluated for inhibition of house-fly M. domestica adults and Cx . quinquefasciatus larvae. Two of the synthesized isoborneol ester derivatives ( 2 and 3 ) showed good activity against both insect species. Additional two derivatives ( 6 and 9 ) were active against M.domestica L. and the derivatives ( 1 – 3 , 8 ) were active against Cx . quinquefasciatus larvae. Isoborneolesters ethers thioethers Musca domestica Culex quinquefasciatus Figures Figure 1 Introduction Many insects affect food production and human health. The housefly is one of the most widely distributed insects that can transmit disease to humans as it is commonly found in homes and restaurants and it is closely associated with humans.The common housefly, Musca domestica L.is considered to be a greater threat to human welfare, than any other species of fly because it can spread diseases with pathogens like diarrhoea, cholera, typhoid, tuberculosis, etc. The diseases that are spread to people by mosquitoes include the Zika virus, West Nile virus, chikungunya virus, dengue, and malaria parasite. As the rate of toxicity is comparatively very high in commercially available pesticides, there is a need to develop an environmentally friendly pesticide. It was also reported by Stevenson (2017) that eco-friendly pesticides are important with promotion of natural products as green pesticides. Isoborneol and borneol are isomeric monoterpenes with a characteristic [2.2.1]bicyclic carbon skeleton. Borneol esters have been found to have larvicidal activity against A. aegypti (Nunes et al. 2018 ). Similarly, borneol and bornyl acetate exhibited LC 50 = 0.073 ppm and 0.035 ppm respectively (Zhang et. al. 2017 ) against Musca domestica L. Two essential oils containing borneol and its acetate among many monoterpenes have been found to possess inhibition of M. domestica adults and Cx . quinquefasciatus larvae (Pavela et al. 2020). Isoborneol displayed 95% of repellent activity at 500 ppm on Subterranean Termites (Blaske et al. 2003 ). Some of the isolated constituents of plant essential oils have been considered to be safer larvicides, as they are easily available and eco-friendly (Silva et al. 2008 ). Cyclic monoterpenoid-like carvacrol (LD 50 = 5500 µg/L) and thymol (LD 50 = 11100 µg/L) have shown moderate activity against Cx. quinquefasciatus third and fourth-stage larvae out of 51 terpenes and terpenoids. Isoborneol (LD 50 = 91900 µg/L) has shown very low activity against Cx. quinquefasciatus larvae compared to the derivatives synthesized in the present work (Rodríguez-Valdez et al. 2018). In this report the synthesis of isoborneol derivatives, and evaluation of their toxicity against M. domestica and Cx. quinquefasciatus are described. Materials and Methods General procedure for Synthesis of Isoborneol esters, ethers and thioethers The isoborneol esters were prepared by nucleophilic substitution reaction according to Sokolova et al. ( 2017 ) with little modification. To a mixture of isoborneol (0.03 mol) and triethylamine (0.03 mol) in 10 mL of dichloromethaneat 0°C under N 2 atmosphere was added various acid chloride (0.05 mol), and the mixture was stirred further at room temperature for 12 h. The organic layer was washed with brine and extracted with dichloromethane. The organic layer was dried over sodium sulfate and the solvent was removed under a vacuum to get pure esters ( 1 – 6 ). The ethers ( 7–9 ) were prepared using Steglich method of adding DCC/DMAP to isoborneol in dichloromethane at 0°C followed by the addition of phenol, thiophenol or methyl thioglycolate respectively. The crude products were purified using a silica gel column (200–400 mesh) and elution with Petrol (B.p. 60–80°C):ethyl acetate mixture (95:05), which yielded pure products. General Characterization Data The isoborneol used for the synthesis of derivatives was obtained from S. H. Kelkar and Company Ltd, Mumbai, India. The synthesized compounds ( 1–9 ) were characterized by spectral analysis. IR spectra were recorded on a Perkin-Elmer Spectrum One instrument, as neat liquids or solids in KBr. 1 H NMR spectra were recorded in CDCl 3 on a Brucker spectrometer at 500 or 400 MHz and 13 C NMR at 125 or 100 MHz at ambient temperature. The NMR chemical shifts are reported in ppm δ related to the TMS signal at 0.00 ppm as an internal reference and the coupling constants (J) are in Hertz (Hz). All the characterization data are available in the Supplementary Material section. Insect rearing and conditions of bioassays The insect species used in this study i.e., Cx . quinquefasciatus larvae (3rd instar), M. domestica adults (3–5 days old) were obtained from an established laboratory colony (Crop Research Institute, Czech Republic, ˃ 20 generations). Both species were reared as described by Benelli et al. (2019). Insecticidal activity on Musca domestica To assess the acute toxicity of isoborneol esters, thioesters and ethers topical applications were done on M. domestica adult females. For insecticidal activity, 1µL of acetone plus the compound at different concentrations of 50, 100, 150, 200, 300, 400, 500µg adult − 1 (each concentration was tested on four groups of 20 flies) were applied to houseflies anesthetized with CO 2 . Acetone was used alone as the negative control. Bornyl acetate was used as a positive control. The negative and positive controls were applied in the same number of treatments on housefly adults. M. domestica individuals were moved to a recovery box (10× 10× 12 cm), with water and sugar as diet, and mortality of the flies was within ordered 24 h of application. Larvicidal activity against Culex quinquefasciatus The acute toxicity of the isoborneol esters, thioesters, and ethers was tested in dimethyl sulphoxide for Cx. quinquefasciatus 3rd instar larvae that were assessed following the WHO procedure (1996) with minor changes (Pavela et al. 2017 ). The tested concentrations were 500, 400, 300, 250, 200, 150, and 100 mg L − 1 , each of these concentrations was replicated four times. The same amount of DMSO dissolved in distilled water as that used for test samples was used as the negative control. Isoborneol was used as a positive control at the same concentration that was used for test samples. The Cx. Quinquefasciatus larvae were transferred into water in the beaker with the above-prepared test solutions (25 larvae/beakers). Four duplicate trials (100 larvae per single replication) were carried out for each sample concentration, and for each trial, a negative control was included. Both the negative and positive controls were applied in the same number of treatments on mosquito larvae. The mortality of the mosquito larvae was recorded after 24 h. Data Analysis Statistics Lethal concentrations (LC 50 , LC 90 ) or the doses (LD 50 , LD 90 ) were calculated using the regression equation, and the 95% confidence limit was calculated using the probit analysis (Finney, 1971 ). Results and Discussion Synthesis In the present work, Isoborneol derivatives were synthesized for determination of their insecticidal activity ( M. domestica ) and larvicidal activity ( Cx. quinquefasciatus ). The isoborneol derivatives were synthesized, as depicted in Fig. 1 , purified by chromatography. The yields of the products ranged from 72% for isoborneolthioacetate ( 8 ) to 90% for isoborneolisobutyrate ( 3 ). All the synthesized compounds were characterized by IR, 1 H NMR, and 13 C NMR spectral analyses. The IR spectra of aliphatic derivatives ( 1 to 3 ) showed the presence of an ester band absorption at 1725–1736 cm − 1 , while the aromatic ester band was at 1709 cm − 1 for 6 and 1728 cm − 1 for 5 . The acyclic ester of isoborneol cyclo-hexane carboxylate ( 4 ) showed the presence of ester peak at 1727 cm − 1 . The thioether derivatives gave a sharp C-S band at 1591 cm − 1 for 7 whereas 1484 cm − 1 for 8 . 1 H NMR of ( 1 – 4 and 6–9 ) showed methane carbon as a doublet of a doublets at 4.63–4.65 ppm and the ester 5 showed a triplet at 4.65 ppm. 13 C NMR exhibited ester C = O peaks between 161–176 ppm for 1 – 6 and the ether C- peak at 84 for 9 .The C-S peaks of 7 and 8 were seen at 44.7 and 47.4 ppm respectively. Structure-Activity The synthesized compounds were evaluated for their insecticidal activity against M. domestica and Cx. quinquefasciatus and the results are summarized in Tables 1 and 2 respectively. Table 1 Mortality of Musca domestica adults(female) as acute toxicity at 24 h after application Compounds Mortality at 200 µg/fly LD50 µg/µL CI95 µg/µL LC90 µg/µL CI95 µg/µL chi p-level Df 1 96.7 ± 2.4 0.107 0.085–0.125 0.191 0.185–0.221 4.134 0.538 5 2 100.0 ± 0.0 0.032 0.029–0.037 0.095 0.082–0.108 5.524 0.237 4 3 100.0 ± 0.0 0.046 0.038–0.051 0.108 0.097–0.123 3.458 0.131 4 4 96.7 ± 2.4 0.078 0.068–0.082 0.189 0.175–0.221 5.215 0.528 4 5 90.0 ± 0.0 0.123 0.115–0.131 0.236 0.199–0.232 3.759 0.269 4 6 96.7 ± 2.4 0.026 0.018–0.029 0.111 0.102–0.122 3.063 0.381 4 7 0.0 ± 0.0 ˃200 8 90.0 ± 0.0 0.130 0.112–0.138 0.218 0.197–0.222 4.782 0.452 3 9 98.3 ± 2.4 0.032 0.025–0.035 0.142 0.135–0.158 0.934 0.865 4 Bornyl acetate 0.035 LC 50 /LD 50 = lethal concentration/dose killing 50% of the exposed population. LC 90 /LD 90 = lethal concentration/dose killing 90% of the exposed population. CI 95 = 95% confidence interval. Table 2 Mortality of Culex quinquefasciatus larvae (3rd instar) as acute toxicity at 24 h after application Compounds Mortality at 500 µg.l − 1 LC 50 (µl.l − 1 ) CI 95 LC 90 (µl.l − 1 ) CI 95 chi p-level Df 1 100.0 ± 0.0 89.1 65.5-116.3 245.5 215.9-259.7 3.209 0.782 6 2 100.0 ± 0.0 110.6 96.7-125.7 296.1 250.1-301.8 4.702 0.451 5 3 100.0 ± 0.0 168.5 135.9-179.9 328.5 311.2-345.6 2.526 0.526 3 4 0.0 ± 0.0 > 500 5 0.0 ± 0.0 ˃500 6 32.8 ± 7.2 ˃500 7 0.0 ± 0.0 ˃500 8 100.0 ± 0.0 46.9 32.8–58.6 76.2 65.7–91.9 0.758 0.912 3 9 32.5 ± 7.2 ˃500 Isoborneol 91.9 (µg.ml − 1 ) LC 50 /LD 50 = lethal concentration/dose killing 50% of the exposed population. LC 90 /LD 90 = lethal concentration/dose killing 90% of the exposed population. CI 95 = 95% confidence interval. It was observed that bornyl acetate was more effective than borneol in insecticidal activity against R. chinesis . Similarly, citronellyl acetate was more effective in fumigant than citronellol against D. melanogaster (Zhang et al. 2016). This showed that the addition of an acetate group increases the toxic effect on the insect species. The aliphatic esters 1 (LC 50 = 0.107 ppm), 2 (LC 50 = 0.032 ppm), and 3 (LC 50 = 0.046 ppm) showed the lowest to highest potency against M. domestica . The compounds 2 and 3 are branched esters. The reverse effect was seen on Cx. quinquefasciatus i.e., 1 (LD 50 = 89.1 µL/L) showed better activity than 2 (LD 50 = 110.6 µL/L) and 3 (LD 50 = 168.5 µL/L) (Table 2 ). The ester-containing aromatic groups, compounds 5 and 7 had very less effect on insects (LC 50 = 0.123 ppm) for 5 but no effect on larvae, It was observed that sulfur-containing compound isoborneol ester 6 showed high activity (LC 50 = 0.026 ppm) with 96.7 mortality at 200 µg/fly on M. domestica and no activity on larvae whereas isoborneol thioether 8 showed high activity on Cx. quinquefasciatus larvae (LD 50 = 46.9 µL/L) and less activity (LC 50 = 130.3 ppm) on M. domestica . Malathion (LC 50 = 0.48 µg/fly) (Kuwano et al. 1982 ) a sulfur-containing organophosphate is a well-known insecticide (US EPA 2009). About one-third of the used pesticides in agriculture contain sulfur and chlorinated compounds (Tomlin 2000 ). However, isoborneol thiophenol ether ( 7 ) did not show any activity on both insect species. The isoborneol-dichlorophenyl ether 9 showed excellent potency (LC 50 = 0.032 ppm) against M. domestica but was not active against larvae. The compound 9 contains two chlorine atoms which might be the reason for its high activity against house flies(Table 1 ). The divergences of units in literature are probably associated with the experimental procedure. The results were for convenience calculated and converted to ppm from µg/fly. Thus, the active compounds can be further used for the development of new insecticidal formulations. A currently valuable benefit of botanical insecticides is that various mechanisms of action guarantee a low risk of developing insect resistance to the active ingredients (Isman et al. 2017 and Jankowska et al. 2019 ). Conclusions We have synthesized 9 derivatives of isoborneol and evaluated them for insecticidal activity against inhibition of house-fly M. domestica L. adults and Cx . quinquefasciatus larvae. We found that compounds 2 (LD 50 = 0.032 ppm), 3 (LD 50 = 0.046 ppm), 6 (LD 50 = 0.026 ppm) and 9 (LD 50 = 0.032 ppm) are effectively active against M. domestica and compounds 1 (LD 50 , 89.1 µg/L), 2 (LD 50 , 110.6 µg/L), 3 (LD 50 , 168.5 µg/L) and 8 (LD 50 = 46.9 µl/L) against Cx . quinquefasciatus larvae. Thus, the esterification of isoborneol has increased the potency in larvicidal activity. However, we are aware that further studies will be required to explain the mechanism of action. Declarations Acknowledgments The authors thank the Kelkar Education Trust, Mumbai, and the Department of Science and Technology, New Delhi, for a FIST grant (Funds for Improvement of Science and Technology Infrastructure in Higher Educational Institutions). R. Pavela would like to thank the Ministry of Agriculture of the Czech Republic for financial support of the botanical pesticide and basic substances research. Ethical Approval- Not Applicable Consent to Participate- Allowed Consent to Publish- Allowed Authors Contributions- S.V.B guided in synthesizing the molecules, M.O.G. synthesized the molecules. P.R. designed and carried out the Insecticidal activity of the molecules. C. R. K. gave synthetic support. S.V.B., M.O.G. analyzed the data and wrote the paper. Funding -Financial support for this work for P.R. was provided by the Ministry of Agriculture of the Czech Republic (Project MZE-RO0418). Competing Interests- Authors declare that there areno competing known financial interests or any personal relationships that could have appeared to influence the work reported in this paper. Availability of data and materials- Further, all the data is available in the main text or supplementary materials. References Ali A, Murphy CC, Demirci B, Wedge DE, Sampson BJ, Khan IA, Baser KHC, Tabanca N (2103) Insecticidal and biting deterrent activity of rose-scented geranium ( Pelargonium spp .) essential oil and individual compounds against Stephanites pyrioides and Aedes aegypti . Pest Manag Sci 69: 1385-1392.doi: 10.1002/ps.3518 Benelli G, Melhorn H (2016) Declining malaria, rising of dengue and Zika virus: Insights for mosquito vector control. Paristol Res 115: 1747-1754. https://doi.org/10.1007/s00436-016-4971-z Benelli G, Pavela R, Petrelli R, Cappellacci L, Santin G, Fiorini D, Sur S, Dall’Acqua S, Canale A (2018) The essential oil from industrial hemp ( Cannabis sativa L. ) by products as an effective tool for insect pest management in organic crops. Ind Crop Prod122: 308-315. https://doi.org/10.1016/j.indcrop.2018.05.032 Benelli G, Pavela R, Zorzetto C, Sanchez-Mateo CC, Santini G, Canale A, Maggi F (2019a) Insecticidal activity of essential oils from Schizogyne sericea (Asteraceae) on four insect pests and two non-target species. Entomol Gen39: 9-18. https://dx.doi.org/10.1127/entomologia/2019/0662 Bernhard L, Bernhard P, Magnussen P (2003) Management of patients with lymphoedema caused by filariasis in North-eastern Tanzania: alternative approaches. Physiotherapy89: 74-749. https://doi.org/10.1016/S0031-9406(05)60500-7 Blaske VU, Hertel H, Forschler BT (2003) Repellent Effects of Isoborneol on Subterranean Termites ( Isoptera:Rhinotermitidae ) in soils of different compositions. J Econ Entomol 96: 1267-1274. https://doi.org/10.1603/0022-0493(2003)096 Finney DJ (1971) Probit Analysis. Cambridge University London, 68-78. FAO (2005) Proceedings of the Asia Regional Workshop Bangkok: Regional Office for Asia and Pacific. Gupta PK (2004) Pesticide exposure-Indian Scene Toxicology 198: 83-90. https://doi.org/10.1016/j.tox.2004.01.021 Ikbal C, Pavela R (2019) Essential oils as active ingredients of botanical insecticides against aphids. Pest Sci92: 971-986. https://link.springer.com/article/10.1007/s10340-019-01089-6 Isman MB (2017) Bridging the gap: moving botanical insecticides from the laboratory to the farm. Ind Crop Prod 110: 10-14. https://doi.org/10.1016/j.indcrop.2017.07.012 Jankowska M, Lapied B, Jankowski W, Stankiewicz M (2019) The usual action of essential oil component, menthol, in potentiating the effect of the carbamate insecticide, bendiocarb. PesticBiochemPhysiol158: 101-111. https://doi.org/10.1016/j.pestbp.2019.04.013 Jasinski P, Zwolak P, Vogel RI, Bodempud, V, Terai K, Galvez J, Land D, Dudek AZ (2011) MT103 inhibits tumor growth with minimal toxicity in murine model of lung carcinoma via induction of apoptosis Invest New Drugs 29: 846-852. https://doi.org/10.1007/s10637-010-9432-4 Kuwano E, Sato N, Eto M (1982) Insecticidal Benzimidazoles with a Terpenoid MoeityAgricul Biol Chem 46: 1715-1716. https://doi.org/10.1080/00021369.1982.10865318 Nunes RKV, Martins NU, Brito BT, Nepel A, Costo VE, Barrson A, Santos LCR, Cavalcanti CHS (2018) Evaluation of (-)-borneol derivatives against the Zika vector, Aedes aegyptia and a non-target species, Artemia sp . Environ Sci Pollut Res Int 25: 31165 – 31174. https://doi.org/10.1007/s11356-018-2809-1 Ochoa SA, Correa-Basurto J, Rodriguez-Valdez LM, Sanchez-Torres LE, Nogueda-Torres B, Nevarez-Moorillon VG (2018)In vitro and in silico studies of terpenes, terpenoids and related compounds with larvicidal and pupaecidal activity against Culex quinquefasciatus Say (Diptera: Culicidae ) Chem Central J 12: 53. https://doi.org/10.1186/s13065-018-0425-2 Pavela R, Maggi F, Kamte SN, Rakotosaona R, Rasoanavo P, Nicoletti M, Canake A, Benelli G (2017) Chemical composition of Cinnamosmamadagascariensis (Cannelaceae) essential oil and its larvicidal potential against the filariasis vector Culex quinquefasciatus Say South Afr J Bot 108: 359-363. https://doi.org/10.1016/j.sajb.2016.08.017 Pav Pavela R, Benelli G, Canale A, Maggi F, Martonfi P (2020) Exploring essential oils of Slovak medicinal plants for insecticidal activity: The case of Thymus alternans and Teucrium montanum subsp. jailae Food and Chemical Toxicology 138: 1-6. https://doi.org/10.1016/j.fct.2020.111203 Palacios SM, Bertoni A, Rossi Y, Moll A (2009) Efficacy of Essential Oils from Edible Plants as Insecticides Against the House Fly, Musa Domestica L. Molecules 14: 1938-1947. https://doi.org/10.3390/molecules14051938 Rahman AA, Bagvan A, Kamraj C, Vadvelu M, Zahir AA, Elango G, Pandiyan G (2009) Evaluation of indigenous plant extracts against larvae of Culex quinquefasciatus Say (Diptera: Culicidae), Paristol Res 104: 67-64. https://doi.org/10.1007/s00436-008-1240-9 Rodríguez‑Valdez LM, Andrarde-Ochoa S, Sanchez-Torres LE, Nogueda-Torres B, Correa-Basurto J, Nevarez-Moorillion GV (2018) In vitro and in silico studies of terpenes, terpenoids and related compounds with larvicidal and pupaecidal activity against Culex quinquefasciatus Say (Diptera: Culicidae). Chem Cent J 12: 53-74. https://doi.org/10.1186/s13065-018-0425-2 Silva WJ, Dória GAA, Maia RT, Nunes RS, Carvalho GA, Blank AF, Alves PB, Marçal RM, Cavalcanti SCH (2008) Effects of essential oils on Aedes aegypti larvae: alternatives to environmentally safe insecticides. Bioresour Technol 99:3251–3255. https://doi.org/10. 1016/j.biortech.2007.05.064 Sokolova AS, Yarovaya OI, Semenova MD, Shtro AA, OrshanskayaYaR, Zarubaev VV, Salakhutdinov NF (2017) Synthesis and in vitro study of the novel borneol derivatives as potent inhibitors of influenza virus. Med Chem Comm 8: 960 – 963. https://doi.org/10.1039%2Fc6md00657d Stevenson PC, Isman MB, Belmain SR (2017) Pesticidal plants in Africa: a global vision of new biological control products from local uses. Ind Crop Prod 110: 2-9. https://doi.org/10.1016/j.indcrop.2017.08.034 Tomlin CDS. (Ed.). (2000) The latest pesticide manual contains 812 chemicals as main entries, 236 (29%) of them are organic or inorganic sulfur compounds The Pesticide Manual (British Crop Protection Council, Farnham, 12 Lamberth C. (2004) Sulphur chemistry in crop protection. J Sulfur Chem 25: 39-62. Vitali LA, Dall’Acqua S, Maggi F, Martonfi P, Papa F, Petrell D, Sut S, Lupid G (2017) Antimicrobial and antioxidant activity of the essential oil from the Carpathian Thymus alternans Klokov Nat Prod Res 31: 1121-1130. https://doi.org/10.1080/14786419.2016.1224874 WHO (1996) Report of the WHO Informal Consultation on the evaluation and testing of Insecticides pp.69 CTD/WHOPES/IC/96.1. Zhang Z, Wang, Y, Wang L, Xie Y, Lin Z (2017) Toxicities of monoterpenes against housefly, Musca domesticaL . (Diptera: Muscidae). Environ Sci Pollut Res 24: 24708-24713. https://doi.org/10.1007/s11356-017-0219-4 Scheme 1 Scheme 1 is available in the Supplementary Files section. Supplementary Files scheme.png Scheme 1: General Mechanism for the synthesis of isoborneol derivatives 2924SUPPORTINGINFOFORINSECTICIDAL24.docx Cite Share Download PDF Status: Published Journal Publication published 23 Aug, 2024 Read the published version in Environmental Science and Pollution Research → Version 1 posted Editorial decision: Major Revision 29 Jun, 2024 Reviewers agreed at journal 20 Mar, 2024 Reviewers invited by journal 15 Mar, 2024 Editor invited by journal 21 Feb, 2024 Editor assigned by journal 05 Feb, 2024 First submitted to journal 28 Jan, 2024 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. 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BHAT","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3ElEQVRIiWNgGAWjYHCCBCC2SeAHMwuI1XKAIS1BsgHENCDWngMMhxMMDoBYxGiRn5Hw8POHmrQ84/OrEz88MGCQ5xc7gF+LwY2EZIkDx2yKzW683SwBdJjhzNkJBLRIJCRIHGBLS9x24+wGkJYEg9sEtAAdlvzjwL/DiZtnnN38gygtDDcS0iQOth1O3MDfu404WwzOPEizONuXVixxg3ebRYKBBGG/yLfnJN+o+GaTx99/dvPNHxU28vzShBzGwANVIQGmJQgpBwH2AxCa/wAxqkfBKBgFo2AkAgD3jkzalet3kgAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0001-8537-4623","institution":"Kelkar Education Trusts V G Vaze College of Arts Science and Commerce","correspondingAuthor":true,"prefix":"","firstName":"SUJATA","middleName":"V.","lastName":"BHAT","suffix":""},{"id":280055835,"identity":"4eb51782-0d62-42bd-83f1-14cf5d4584d2","order_by":1,"name":"Manisha O. Gupta","email":"","orcid":"","institution":"V G Vaze College: Kelkar Education Trusts V G Vaze College of Arts Science and Commerce","correspondingAuthor":false,"prefix":"","firstName":"Manisha","middleName":"O.","lastName":"Gupta","suffix":""},{"id":280055836,"identity":"5878a999-40c3-4b27-87e7-a73c95aa1c5a","order_by":2,"name":"Roman Pavela","email":"","orcid":"","institution":"Crop Research Institute Dmvoska Prague,6 Czech Republic","correspondingAuthor":false,"prefix":"","firstName":"Roman","middleName":"","lastName":"Pavela","suffix":""},{"id":280055837,"identity":"3a1152b3-347f-46ad-8260-02ea8cfa01bd","order_by":3,"name":"Chitra R. Kamath","email":"","orcid":"","institution":"S K Somaiya College of Arts Science and Commerce","correspondingAuthor":false,"prefix":"","firstName":"Chitra","middleName":"R.","lastName":"Kamath","suffix":""}],"badges":[],"createdAt":"2024-01-06 10:16:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3839460/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3839460/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s11356-024-34719-3","type":"published","date":"2024-08-23T15:58:06+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":53004110,"identity":"508923d5-da1e-4002-b892-33938c88f594","added_by":"auto","created_at":"2024-03-19 14:49:15","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":30165,"visible":true,"origin":"","legend":"\u003cp\u003eSynthesis of Isoborneol derivatives.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3839460/v1/65b76bd2691f997008e5f0b5.png"},{"id":63300450,"identity":"dcd7c22d-00df-4537-a747-1bd9afe23848","added_by":"auto","created_at":"2024-08-26 16:14:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":652292,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3839460/v1/7e308674-9278-41c8-a995-75e07fd6c8c8.pdf"},{"id":53004111,"identity":"5969ea7d-2ccb-42e9-8193-d78901aed1b2","added_by":"auto","created_at":"2024-03-19 14:49:15","extension":"png","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":9955,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eScheme 1\u003c/strong\u003e: General Mechanism for the synthesis of isoborneol derivatives\u003c/p\u003e","description":"","filename":"scheme.png","url":"https://assets-eu.researchsquare.com/files/rs-3839460/v1/d97fe3330e9c0224fbbca2a1.png"},{"id":53004115,"identity":"eabf2435-354a-4aee-b9d8-ff6bbabfcad0","added_by":"auto","created_at":"2024-03-19 14:49:16","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":5433355,"visible":true,"origin":"","legend":"","description":"","filename":"2924SUPPORTINGINFOFORINSECTICIDAL24.docx","url":"https://assets-eu.researchsquare.com/files/rs-3839460/v1/37e42ec5d1172eff323b545d.docx"}],"financialInterests":"","formattedTitle":"Insecticidal activity of isoborneol derivatives against Musca domestica adults and Culex quinquefasciatus larvae","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMany insects affect food production and human health. The housefly is one of the most widely distributed insects that can transmit disease to humans as it is commonly found in homes and restaurants and it is closely associated with humans.The common housefly,\u003cem\u003eMusca domestica\u003c/em\u003e L.is considered to be a greater threat to human welfare, than any other species of fly because it can spread diseases with pathogens like diarrhoea, cholera, typhoid, tuberculosis, etc. The diseases that are spread to people by mosquitoes include the Zika virus, West Nile virus, chikungunya virus, dengue, and malaria parasite.\u003c/p\u003e \u003cp\u003eAs the rate of toxicity is comparatively very high in commercially available pesticides, there is a need to develop an environmentally friendly pesticide. It was also reported by Stevenson (2017) that eco-friendly pesticides are important with promotion of natural products as green pesticides.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIsoborneol and borneol are isomeric monoterpenes with a characteristic [2.2.1]bicyclic carbon skeleton. Borneol esters have been found to have larvicidal activity against \u003cem\u003eA. aegypti\u003c/em\u003e (Nunes et al. \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). Similarly, borneol and bornyl acetate exhibited LC\u003csub\u003e50\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;0.073 ppm and 0.035 ppm respectively (Zhang et. al. \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e2017\u003c/span\u003e) against \u003cem\u003eMusca domestica\u003c/em\u003e L. Two essential oils containing borneol and its acetate among many monoterpenes have been found to possess inhibition of \u003cem\u003eM. domestica\u003c/em\u003e adults and \u003cem\u003eCx\u003c/em\u003e. \u003cem\u003equinquefasciatus\u003c/em\u003e larvae (Pavela \u003cem\u003eet al.\u003c/em\u003e 2020). Isoborneol displayed 95% of repellent activity at 500 ppm on Subterranean Termites (Blaske et al. \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2003\u003c/span\u003e). Some of the isolated constituents of plant essential oils have been considered to be safer larvicides, as they are easily available and eco-friendly (Silva et al. \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2008\u003c/span\u003e). Cyclic monoterpenoid-like carvacrol (LD\u003csub\u003e50\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;5500 \u0026micro;g/L) and thymol (LD\u003csub\u003e50\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;11100 \u0026micro;g/L) have shown moderate activity against \u003cem\u003eCx. quinquefasciatus\u003c/em\u003e third and fourth-stage larvae out of 51 terpenes and terpenoids. Isoborneol (LD\u003csub\u003e50\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;91900 \u0026micro;g/L) has shown very low activity against Cx. quinquefasciatus larvae compared to the derivatives synthesized in the present work (Rodr\u0026iacute;guez-Valdez et al. 2018).\u003c/p\u003e \u003cp\u003eIn this report the synthesis of isoborneol derivatives, and evaluation of their toxicity against \u003cem\u003eM. domestica\u003c/em\u003e and \u003cem\u003eCx. quinquefasciatus\u003c/em\u003e are described.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eGeneral procedure for Synthesis of Isoborneol esters, ethers and thioethers\u003c/h2\u003e \u003cp\u003eThe isoborneol esters were prepared by nucleophilic substitution reaction according to Sokolova et al. (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2017\u003c/span\u003e) with little modification. To a mixture of isoborneol (0.03 mol) and triethylamine (0.03 mol) in 10 mL of dichloromethaneat 0\u0026deg;C under N\u003csub\u003e2\u003c/sub\u003e atmosphere was added various acid chloride (0.05 mol), and the mixture was stirred further at room temperature for 12 h. The organic layer was washed with brine and extracted with dichloromethane. The organic layer was dried over sodium sulfate and the solvent was removed under a vacuum to get pure esters (\u003cb\u003e1\u003c/b\u003e\u0026ndash;\u003cb\u003e6\u003c/b\u003e). The ethers (\u003cb\u003e7\u0026ndash;9\u003c/b\u003e) were prepared using Steglich method of adding DCC/DMAP to isoborneol in dichloromethane at 0\u0026deg;C followed by the addition of phenol, thiophenol or methyl thioglycolate respectively. The crude products were purified using a silica gel column (200\u0026ndash;400 mesh) and elution with Petrol (B.p. 60\u0026ndash;80\u0026deg;C):ethyl acetate mixture (95:05), which yielded pure products.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eGeneral Characterization Data\u003c/h2\u003e \u003cp\u003eThe isoborneol used for the synthesis of derivatives was obtained from S. H. Kelkar and Company Ltd, Mumbai, India. The synthesized compounds (\u003cb\u003e1\u0026ndash;9\u003c/b\u003e) were characterized by spectral analysis. IR spectra were recorded on a Perkin-Elmer Spectrum One instrument, as neat liquids or solids in KBr. \u003csup\u003e1\u003c/sup\u003eH NMR spectra were recorded in CDCl\u003csub\u003e3\u003c/sub\u003e on a Brucker spectrometer at 500 or 400 MHz and \u003csup\u003e13\u003c/sup\u003eC NMR at 125 or 100 MHz at ambient temperature. The NMR chemical shifts are reported in ppm δ related to the TMS signal at 0.00 ppm as an internal reference and the coupling constants (J) are in Hertz (Hz). All the characterization data are available in the Supplementary Material section.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eInsect rearing and conditions of bioassays\u003c/h2\u003e \u003cp\u003eThe insect species used in this study i.e., \u003cem\u003eCx\u003c/em\u003e. \u003cem\u003equinquefasciatus\u003c/em\u003e larvae (3rd instar), \u003cem\u003eM. domestica\u003c/em\u003e adults (3\u0026ndash;5 days old) were obtained from an established laboratory colony (Crop Research Institute, Czech Republic, ˃ 20 generations). Both species were reared as described by Benelli \u003cem\u003eet al.\u003c/em\u003e (2019).\u003c/p\u003e \u003cp\u003e \u003cb\u003eInsecticidal activity on\u003c/b\u003e \u003cb\u003eMusca domestica\u003c/b\u003e\u003c/p\u003e \u003cp\u003eTo assess the acute toxicity of isoborneol esters, thioesters and ethers topical applications were done on \u003cem\u003eM. domestica\u003c/em\u003e adult females. For insecticidal activity, 1\u0026micro;L of acetone plus the compound at different concentrations of 50, 100, 150, 200, 300, 400, 500\u0026micro;g adult\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e (each concentration was tested on four groups of 20 flies) were applied to houseflies anesthetized with CO\u003csub\u003e2\u003c/sub\u003e. Acetone was used alone as the negative control. Bornyl acetate was used as a positive control. The negative and positive controls were applied in the same number of treatments on housefly adults. \u003cem\u003eM. domestica\u003c/em\u003e individuals were moved to a recovery box (10\u0026times; 10\u0026times; 12 cm), with water and sugar as diet, and mortality of the flies was within ordered 24 h of application.\u003c/p\u003e \u003cp\u003e \u003cb\u003eLarvicidal activity against\u003c/b\u003e \u003cb\u003eCulex quinquefasciatus\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe acute toxicity of the isoborneol esters, thioesters, and ethers was tested in dimethyl sulphoxide for \u003cem\u003eCx. quinquefasciatus\u003c/em\u003e 3rd instar larvae that were assessed following the WHO procedure (1996) with minor changes (Pavela et al. \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). The tested concentrations were 500, 400, 300, 250, 200, 150, and 100 mg L\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e, each of these concentrations was replicated four times. The same amount of DMSO dissolved in distilled water as that used for test samples was used as the negative control. Isoborneol was used as a positive control at the same concentration that was used for test samples. The \u003cem\u003eCx. Quinquefasciatus\u003c/em\u003e larvae were transferred into water in the beaker with the above-prepared test solutions (25 larvae/beakers). Four duplicate trials (100 larvae per single replication) were carried out for each sample concentration, and for each trial, a negative control was included. Both the negative and positive controls were applied in the same number of treatments on mosquito larvae. The mortality of the mosquito larvae was recorded after 24 h.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eData Analysis\u003c/h2\u003e \u003cdiv id=\"Sec7\" class=\"Section3\"\u003e \u003ch2\u003eStatistics\u003c/h2\u003e \u003cp\u003eLethal concentrations (LC\u003csub\u003e50\u003c/sub\u003e, LC\u003csub\u003e90\u003c/sub\u003e) or the doses (LD\u003csub\u003e50\u003c/sub\u003e, LD\u003csub\u003e90\u003c/sub\u003e) were calculated using the regression equation, and the 95% confidence limit was calculated using the probit analysis (Finney, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e1971\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Results and Discussion","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eSynthesis\u003c/h2\u003e \u003cp\u003eIn the present work, Isoborneol derivatives were synthesized for determination of their insecticidal activity (\u003cem\u003eM. domestica\u003c/em\u003e) and larvicidal activity (\u003cem\u003eCx. quinquefasciatus\u003c/em\u003e). The isoborneol derivatives were synthesized, as depicted in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, purified by chromatography. The yields of the products ranged from 72% for isoborneolthioacetate (\u003cb\u003e8\u003c/b\u003e) to 90% for isoborneolisobutyrate (\u003cb\u003e3\u003c/b\u003e). All the synthesized compounds were characterized by IR, \u003csup\u003e1\u003c/sup\u003eH NMR, and \u003csup\u003e13\u003c/sup\u003eC NMR spectral analyses.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe IR spectra of aliphatic derivatives (\u003cb\u003e1\u003c/b\u003e to \u003cb\u003e3\u003c/b\u003e) showed the presence of an ester band absorption at 1725\u0026ndash;1736 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e, while the aromatic ester band was at 1709 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e for \u003cb\u003e6\u003c/b\u003e and 1728 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e for \u003cb\u003e5\u003c/b\u003e. The acyclic ester of isoborneol cyclo-hexane carboxylate (\u003cb\u003e4\u003c/b\u003e) showed the presence of ester peak at 1727 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e. The thioether derivatives gave a sharp C-S band at 1591 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e for \u003cb\u003e7\u003c/b\u003e whereas 1484 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e for \u003cb\u003e8\u003c/b\u003e. \u003csup\u003e1\u003c/sup\u003eH NMR of (\u003cb\u003e1\u003c/b\u003e\u0026ndash;\u003cb\u003e4\u003c/b\u003e and \u003cb\u003e6\u0026ndash;9\u003c/b\u003e) showed methane carbon as a doublet of a doublets at 4.63\u0026ndash;4.65 ppm and the ester \u003cb\u003e5\u003c/b\u003e showed a triplet at 4.65 ppm. \u003csup\u003e13\u003c/sup\u003eC NMR exhibited ester C\u0026thinsp;=\u0026thinsp;O peaks between 161\u0026ndash;176 ppm for \u003cb\u003e1\u003c/b\u003e\u0026ndash;\u003cb\u003e6\u003c/b\u003e and the ether C- peak at 84 for \u003cb\u003e9\u003c/b\u003e.The C-S peaks of \u003cb\u003e7\u003c/b\u003e and \u003cb\u003e8\u003c/b\u003e were seen at 44.7 and 47.4 ppm respectively.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eStructure-Activity\u003c/h2\u003e \u003cp\u003eThe synthesized compounds were evaluated for their insecticidal activity against \u003cem\u003eM. domestica\u003c/em\u003e and \u003cem\u003eCx. quinquefasciatus\u003c/em\u003e and the results are summarized in Tables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e respectively.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMortality of \u003cem\u003eMusca domestica\u003c/em\u003e adults(female) as acute toxicity at 24 h after application\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCompounds\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMortality at 200 \u0026micro;g/fly\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLD50\u003c/p\u003e \u003cp\u003e\u0026micro;g/\u0026micro;L\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCI95\u003c/p\u003e \u003cp\u003e\u0026micro;g/\u0026micro;L\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLC90\u003c/p\u003e \u003cp\u003e\u0026micro;g/\u0026micro;L\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCI95\u003c/p\u003e \u003cp\u003e\u0026micro;g/\u0026micro;L\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003echi\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003ep-level\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eDf\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e96.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.107\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.085\u0026ndash;0.125\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.191\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.185\u0026ndash;0.221\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4.134\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.538\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e100.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.032\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.029\u0026ndash;0.037\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.095\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.082\u0026ndash;0.108\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e5.524\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.237\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e100.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.046\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.038\u0026ndash;0.051\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.108\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.097\u0026ndash;0.123\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e3.458\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.131\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e96.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.078\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.068\u0026ndash;0.082\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.189\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.175\u0026ndash;0.221\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e5.215\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.528\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e90.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.123\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.115\u0026ndash;0.131\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.236\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.199\u0026ndash;0.232\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e3.759\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.269\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e96.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.026\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.018\u0026ndash;0.029\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.111\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.102\u0026ndash;0.122\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e3.063\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.381\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e˃200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e90.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.130\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.112\u0026ndash;0.138\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.218\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.197\u0026ndash;0.222\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4.782\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.452\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e98.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.032\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.025\u0026ndash;0.035\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.142\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.135\u0026ndash;0.158\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.934\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.865\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBornyl acetate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.035\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eLC\u003csub\u003e50\u003c/sub\u003e/LD\u003csub\u003e50\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;lethal concentration/dose killing 50% of the exposed population.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eLC\u003csub\u003e90\u003c/sub\u003e/LD\u003csub\u003e90\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;lethal concentration/dose killing 90% of the exposed population.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eCI\u003csub\u003e95\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;95% confidence interval.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMortality of \u003cem\u003eCulex quinquefasciatus\u003c/em\u003e larvae (3rd instar) as acute toxicity at 24 h after application\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCompounds\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMortality at 500 \u0026micro;g.l\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLC\u003csub\u003e50\u003c/sub\u003e\u003c/p\u003e \u003cp\u003e(\u0026micro;l.l\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCI\u003csub\u003e95\u003c/sub\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLC\u003csub\u003e90\u003c/sub\u003e\u003c/p\u003e \u003cp\u003e(\u0026micro;l.l\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCI\u003csub\u003e95\u003c/sub\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003echi\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003ep-level\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eDf\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e100.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e89.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e65.5-116.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e245.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e215.9-259.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e3.209\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.782\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e100.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e110.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e96.7-125.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e296.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e250.1-301.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4.702\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.451\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e100.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e168.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e135.9-179.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e328.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e311.2-345.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2.526\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.526\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;500\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e˃500\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e32.8\u0026thinsp;\u0026plusmn;\u0026thinsp;7.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e˃500\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e˃500\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e100.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32.8\u0026ndash;58.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e76.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e65.7\u0026ndash;91.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.758\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.912\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e32.5\u0026thinsp;\u0026plusmn;\u0026thinsp;7.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e˃500\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIsoborneol\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e91.9\u003c/p\u003e \u003cp\u003e(\u0026micro;g.ml\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eLC\u003csub\u003e50\u003c/sub\u003e/LD\u003csub\u003e50\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;lethal concentration/dose killing 50% of the exposed population.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eLC\u003csub\u003e90\u003c/sub\u003e/LD\u003csub\u003e90\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;lethal concentration/dose killing 90% of the exposed population.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eCI\u003csub\u003e95\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;95% confidence interval.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIt was observed that bornyl acetate was more effective than borneol in insecticidal activity against \u003cem\u003eR. chinesis\u003c/em\u003e. Similarly, citronellyl acetate was more effective in fumigant than citronellol against \u003cem\u003eD. melanogaster\u003c/em\u003e (Zhang et al. 2016). This showed that the addition of an acetate group increases the toxic effect on the insect species.\u003c/p\u003e \u003cp\u003eThe aliphatic esters \u003cb\u003e1\u003c/b\u003e (LC\u003csub\u003e50\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;0.107 ppm), \u003cb\u003e2\u003c/b\u003e (LC\u003csub\u003e50\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;0.032 ppm), and \u003cb\u003e3\u003c/b\u003e (LC\u003csub\u003e50\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;0.046 ppm) showed the lowest to highest potency against \u003cem\u003eM. domestica\u003c/em\u003e. The compounds \u003cb\u003e2\u003c/b\u003e and \u003cb\u003e3\u003c/b\u003e are branched esters. The reverse effect was seen on \u003cem\u003eCx. quinquefasciatus\u003c/em\u003e i.e., \u003cb\u003e1\u003c/b\u003e (LD\u003csub\u003e50\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;89.1 \u0026micro;L/L) showed better activity than \u003cb\u003e2\u003c/b\u003e (LD\u003csub\u003e50\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;110.6 \u0026micro;L/L) and \u003cb\u003e3\u003c/b\u003e (LD\u003csub\u003e50\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;168.5 \u0026micro;L/L) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe ester-containing aromatic groups, compounds \u003cb\u003e5\u003c/b\u003e and \u003cb\u003e7\u003c/b\u003e had very less effect on insects (LC\u003csub\u003e50\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;0.123 ppm) for \u003cb\u003e5\u003c/b\u003e but no effect on larvae, It was observed that sulfur-containing compound isoborneol ester \u003cb\u003e6\u003c/b\u003e showed high activity (LC\u003csub\u003e50\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;0.026 ppm) with 96.7 mortality at 200 \u0026micro;g/fly on \u003cem\u003eM. domestica\u003c/em\u003e and no activity on larvae whereas isoborneol thioether \u003cb\u003e8\u003c/b\u003e showed high activity on \u003cem\u003eCx. quinquefasciatus\u003c/em\u003e larvae (LD\u003csub\u003e50\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;46.9 \u0026micro;L/L) and less activity (LC\u003csub\u003e50\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;130.3 ppm) on \u003cem\u003eM. domestica\u003c/em\u003e. Malathion (LC\u003csub\u003e50\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;0.48 \u0026micro;g/fly) (Kuwano et al. \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e1982\u003c/span\u003e) a sulfur-containing organophosphate is a well-known insecticide (US EPA 2009). About one-third of the used pesticides in agriculture contain sulfur and chlorinated compounds (Tomlin \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2000\u003c/span\u003e). However, isoborneol thiophenol ether (\u003cb\u003e7\u003c/b\u003e) did not show any activity on both insect species. The isoborneol-dichlorophenyl ether \u003cb\u003e9\u003c/b\u003e showed excellent potency (LC\u003csub\u003e50\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;0.032 ppm) against \u003cem\u003eM. domestica\u003c/em\u003e but was not active against larvae. The compound \u003cb\u003e9\u003c/b\u003e contains two chlorine atoms which might be the reason for its high activity against house flies(Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe divergences of units in literature are probably associated with the experimental procedure. The results were for convenience calculated and converted to ppm from \u0026micro;g/fly.\u003c/p\u003e \u003cp\u003eThus, the active compounds can be further used for the development of new insecticidal formulations.\u003c/p\u003e \u003cp\u003eA currently valuable benefit of botanical insecticides is that various mechanisms of action guarantee a low risk of developing insect resistance to the active ingredients (Isman et al. 2017 and Jankowska et al. \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2019\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eWe have synthesized 9 derivatives of isoborneol and evaluated them for insecticidal activity against inhibition of house-fly \u003cem\u003eM. domestica\u003c/em\u003e L. adults and \u003cem\u003eCx\u003c/em\u003e.\u003cem\u003equinquefasciatus\u003c/em\u003e larvae.\u003c/p\u003e \u003cp\u003eWe found that compounds \u003cb\u003e2\u003c/b\u003e (LD\u003csub\u003e50\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;0.032 ppm), \u003cb\u003e3\u003c/b\u003e (LD\u003csub\u003e50\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;0.046 ppm), \u003cb\u003e6\u003c/b\u003e (LD\u003csub\u003e50\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;0.026 ppm) and \u003cb\u003e9\u003c/b\u003e (LD\u003csub\u003e50\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;0.032 ppm) are effectively active against \u003cem\u003eM. domestica\u003c/em\u003e and compounds \u003cb\u003e1\u003c/b\u003e (LD\u003csub\u003e50\u003c/sub\u003e, 89.1 \u0026micro;g/L), \u003cb\u003e2\u003c/b\u003e (LD\u003csub\u003e50\u003c/sub\u003e, 110.6 \u0026micro;g/L), \u003cb\u003e3\u003c/b\u003e (LD\u003csub\u003e50\u003c/sub\u003e, 168.5 \u0026micro;g/L) and \u003cb\u003e8\u003c/b\u003e (LD\u003csub\u003e50\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;46.9 \u0026micro;l/L) against \u003cem\u003eCx\u003c/em\u003e. \u003cem\u003equinquefasciatus\u003c/em\u003elarvae. Thus, the esterification of isoborneol has increased the potency in larvicidal activity. However, we are aware that further studies will be required to explain the mechanism of action.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u0026nbsp;\u003c/strong\u003eThe authors thank the Kelkar Education Trust, Mumbai, and the Department of Science and Technology, New Delhi, for a FIST grant (Funds for Improvement of Science and Technology Infrastructure in Higher Educational Institutions). R. Pavela would like to thank the Ministry of Agriculture of the Czech Republic for financial support of the botanical pesticide and basic substances research.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Approval-\u003c/strong\u003e Not Applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Participate-\u003c/strong\u003e Allowed\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eConsent to Publish-\u003c/strong\u003e Allowed\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors Contributions-\u003c/strong\u003eS.V.B guided in synthesizing the molecules, M.O.G. synthesized the molecules. P.R. designed and carried out the Insecticidal activity of the molecules. C. R. K. gave synthetic support. S.V.B., M.O.G. analyzed the data and wrote the paper.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eFunding\u003c/strong\u003e -Financial support for this work for P.R. was provided by the Ministry of Agriculture of the Czech Republic (Project MZE-RO0418).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests-\u003c/strong\u003eAuthors declare that there areno competing known financial interests or any personal relationships that could have appeared to influence the work reported in this paper.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials-\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFurther, all the data is available in the main text or supplementary materials.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAli A, Murphy CC, Demirci B, Wedge DE, Sampson BJ, Khan IA, Baser KHC, Tabanca N (2103) Insecticidal and biting deterrent activity of rose-scented geranium (\u003cem\u003ePelargonium spp\u003c/em\u003e.) essential oil and individual compounds against Stephanites pyrioides and \u003cem\u003eAedes aegypti\u003c/em\u003e. Pest Manag Sci 69: 1385-1392.doi: 10.1002/ps.3518\u003c/li\u003e\n\u003cli\u003eBenelli G, Melhorn H (2016) Declining malaria, rising of dengue and \u003cem\u003eZika\u003c/em\u003e virus: Insights for mosquito vector control. Paristol Res 115: 1747-1754. https://doi.org/10.1007/s00436-016-4971-z\u003c/li\u003e\n\u003cli\u003eBenelli G, Pavela R, Petrelli R, Cappellacci L, Santin G, Fiorini D, Sur S, Dall\u0026rsquo;Acqua S, Canale A (2018) The essential oil from industrial hemp (\u003cem\u003eCannabis sativa L.\u003c/em\u003e) by products as an effective tool for insect pest management in organic crops. Ind Crop Prod122: 308-315. https://doi.org/10.1016/j.indcrop.2018.05.032\u003c/li\u003e\n\u003cli\u003eBenelli G, Pavela R, Zorzetto C, Sanchez-Mateo CC, Santini G, Canale A, Maggi F (2019a) Insecticidal activity of essential oils from \u003cem\u003eSchizogyne sericea\u003c/em\u003e (Asteraceae) on four insect pests and two non-target species. Entomol Gen39: 9-18. https://dx.doi.org/10.1127/entomologia/2019/0662\u003c/li\u003e\n\u003cli\u003eBernhard L, Bernhard P, Magnussen P (2003) Management of patients with lymphoedema caused by filariasis in North-eastern Tanzania: alternative approaches. Physiotherapy89: 74-749. https://doi.org/10.1016/S0031-9406(05)60500-7\u003c/li\u003e\n\u003cli\u003eBlaske VU, Hertel H, Forschler BT (2003) Repellent Effects of Isoborneol on Subterranean Termites (\u003cem\u003eIsoptera:Rhinotermitidae\u003c/em\u003e) in soils of different compositions. J Econ Entomol 96: 1267-1274. https://doi.org/10.1603/0022-0493(2003)096\u003c/li\u003e\n\u003cli\u003eFinney DJ (1971) Probit Analysis. Cambridge University London, 68-78.\u003c/li\u003e\n\u003cli\u003eFAO (2005) Proceedings of the Asia Regional Workshop Bangkok: Regional Office for Asia and Pacific.\u003c/li\u003e\n\u003cli\u003eGupta PK (2004) Pesticide exposure-Indian Scene Toxicology 198: 83-90. https://doi.org/10.1016/j.tox.2004.01.021\u003c/li\u003e\n\u003cli\u003eIkbal C, Pavela R (2019) Essential oils as active ingredients of botanical insecticides against aphids. Pest Sci92: 971-986. https://link.springer.com/article/10.1007/s10340-019-01089-6\u003c/li\u003e\n\u003cli\u003eIsman MB (2017) Bridging the gap: moving botanical insecticides from the laboratory to the farm. Ind Crop Prod 110: 10-14. https://doi.org/10.1016/j.indcrop.2017.07.012\u003c/li\u003e\n\u003cli\u003eJankowska M, Lapied B, Jankowski W, Stankiewicz M (2019) The usual action of essential oil component, menthol, in potentiating the effect of the carbamate insecticide, bendiocarb. PesticBiochemPhysiol158: 101-111. https://doi.org/10.1016/j.pestbp.2019.04.013\u003c/li\u003e\n\u003cli\u003eJasinski P, Zwolak P, Vogel RI, Bodempud, V, Terai K, Galvez J, Land D, Dudek AZ (2011) MT103 inhibits tumor growth with minimal toxicity in murine model of lung carcinoma via induction of apoptosis Invest New Drugs 29: 846-852. https://doi.org/10.1007/s10637-010-9432-4\u003c/li\u003e\n\u003cli\u003eKuwano E, Sato N, Eto M (1982) Insecticidal Benzimidazoles with a Terpenoid MoeityAgricul Biol Chem 46: 1715-1716. https://doi.org/10.1080/00021369.1982.10865318\u003c/li\u003e\n\u003cli\u003eNunes RKV, Martins NU, Brito BT, Nepel A, Costo VE, Barrson A, Santos LCR, Cavalcanti CHS (2018) Evaluation of (-)-borneol derivatives against the Zika vector, \u003cem\u003eAedes aegyptia\u003c/em\u003e and a non-target species, \u003cem\u003eArtemia sp\u003c/em\u003e. Environ Sci Pollut Res Int 25: 31165 \u0026ndash; 31174. https://doi.org/10.1007/s11356-018-2809-1\u003c/li\u003e\n\u003cli\u003eOchoa SA, Correa-Basurto J, Rodriguez-Valdez LM, Sanchez-Torres LE, Nogueda-Torres B, Nevarez-Moorillon VG (2018)In vitro and in silico studies of terpenes, terpenoids and related compounds with larvicidal and pupaecidal activity against \u003cem\u003eCulex quinquefasciatus\u003c/em\u003e Say (Diptera: \u003cem\u003eCulicidae\u003c/em\u003e) Chem Central J 12: 53. https://doi.org/10.1186/s13065-018-0425-2\u003c/li\u003e\n\u003cli\u003ePavela R, Maggi F, Kamte SN, Rakotosaona R, Rasoanavo P, Nicoletti M, Canake A, Benelli G (2017) Chemical composition of \u003cem\u003eCinnamosmamadagascariensis\u003c/em\u003e(Cannelaceae) essential oil and its larvicidal potential against the filariasis vector Culex quinquefasciatus Say South Afr J Bot 108: 359-363. https://doi.org/10.1016/j.sajb.2016.08.017\u003c/li\u003e\n\u003cli\u003ePav Pavela R, Benelli G, Canale A, Maggi F, Martonfi P (2020) Exploring essential oils of Slovak medicinal plants for insecticidal activity: The case of \u003cem\u003eThymus alternans\u003c/em\u003e and \u003cem\u003eTeucrium montanum\u003c/em\u003e subsp. \u003cem\u003ejailae\u003c/em\u003eFood and Chemical Toxicology 138: 1-6. https://doi.org/10.1016/j.fct.2020.111203\u003c/li\u003e\n\u003cli\u003ePalacios SM, Bertoni A, Rossi Y, Moll A (2009) Efficacy of Essential Oils from Edible Plants as Insecticides Against the House Fly, \u003cem\u003eMusa Domestica \u003c/em\u003eL. Molecules 14: 1938-1947. https://doi.org/10.3390/molecules14051938\u003c/li\u003e\n\u003cli\u003eRahman AA, Bagvan A, Kamraj C, Vadvelu M, Zahir AA, Elango G, Pandiyan G (2009) Evaluation of indigenous plant extracts against larvae of \u003cem\u003eCulex quinquefasciatus\u003c/em\u003e Say (Diptera: Culicidae), Paristol Res 104: 67-64. https://doi.org/10.1007/s00436-008-1240-9\u003c/li\u003e\n\u003cli\u003eRodr\u0026iacute;guez‑Valdez LM, Andrarde-Ochoa S, Sanchez-Torres LE, Nogueda-Torres B, Correa-Basurto J, Nevarez-Moorillion GV (2018) In vitro and in silico studies of terpenes, terpenoids and related compounds with larvicidal and pupaecidal activity against \u003cem\u003eCulex quinquefasciatus\u003c/em\u003e Say (Diptera: Culicidae). Chem Cent J 12: 53-74. https://doi.org/10.1186/s13065-018-0425-2\u003c/li\u003e\n\u003cli\u003eSilva WJ, D\u0026oacute;ria GAA, Maia RT, Nunes RS, Carvalho GA, Blank AF, Alves PB, Mar\u0026ccedil;al RM, Cavalcanti SCH (2008) Effects of essential oils on Aedes aegypti larvae: alternatives to environmentally safe insecticides. Bioresour Technol 99:3251\u0026ndash;3255. https://doi.org/10. 1016/j.biortech.2007.05.064\u003c/li\u003e\n\u003cli\u003eSokolova AS, Yarovaya OI, Semenova MD, Shtro AA, OrshanskayaYaR, Zarubaev VV, Salakhutdinov NF (2017) Synthesis and in vitro study of the novel borneol derivatives as potent inhibitors of influenza virus. Med Chem Comm 8: 960 \u0026ndash; 963. https://doi.org/10.1039%2Fc6md00657d\u003c/li\u003e\n\u003cli\u003eStevenson PC, Isman MB, Belmain SR (2017) Pesticidal plants in Africa: a global vision of new biological control products from local uses. Ind Crop Prod 110: 2-9. https://doi.org/10.1016/j.indcrop.2017.08.034\u003c/li\u003e\n\u003cli\u003eTomlin CDS. (Ed.). (2000) The latest pesticide manual contains 812 chemicals as main entries, 236 (29%) of them are organic or inorganic sulfur compounds The Pesticide Manual (British Crop Protection Council, Farnham, 12 Lamberth C. (2004) Sulphur chemistry in crop protection. J Sulfur Chem 25: 39-62.\u003c/li\u003e\n\u003cli\u003eVitali LA, Dall\u0026rsquo;Acqua S, Maggi F, Martonfi P, Papa F, Petrell D, Sut S, Lupid G (2017) Antimicrobial and antioxidant activity of the essential oil from the \u003cem\u003eCarpathian Thymus alternans\u003c/em\u003eKlokov Nat Prod Res 31: 1121-1130. https://doi.org/10.1080/14786419.2016.1224874\u003c/li\u003e\n\u003cli\u003eWHO (1996) Report of the WHO Informal Consultation on the evaluation and testing of Insecticides pp.69 CTD/WHOPES/IC/96.1.\u003c/li\u003e\n\u003cli\u003eZhang Z, Wang, Y, Wang L, Xie Y, Lin Z (2017) Toxicities of monoterpenes against housefly, \u003cem\u003eMusca domesticaL\u003c/em\u003e. (Diptera: Muscidae). Environ Sci Pollut Res 24: 24708-24713. https://doi.org/10.1007/s11356-017-0219-4\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Scheme 1","content":"\u003cp\u003eScheme 1 is available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"environmental-science-and-pollution-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"espr","sideBox":"Learn more about [Environmental Science and Pollution Research](https://www.springer.com/journal/11356)","snPcode":"11356","submissionUrl":"https://submission.nature.com/new-submission/11356/3","title":"Environmental Science and Pollution Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Isoborneolesters, ethers, thioethers, Musca domestica, Culex quinquefasciatus","lastPublishedDoi":"10.21203/rs.3.rs-3839460/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3839460/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e \u003cem\u003eMusca domestica L.\u003c/em\u003e, a common housefly, and \u003cem\u003eCulex quinquefasciatus\u003c/em\u003e mosquito are quite well-known pests that can transfer a wide range of diseases to humans as well as animals. In this study, various isoborneol derivatives including esters, ethers and thioethers were synthesized fromisoborneol under mild conditions. These derivatives were evaluated for inhibition of house-fly \u003cem\u003eM. domestica\u003c/em\u003e adults and \u003cem\u003eCx\u003c/em\u003e. \u003cem\u003equinquefasciatus\u003c/em\u003e larvae. Two of the synthesized isoborneol ester derivatives (\u003cb\u003e2\u003c/b\u003e and \u003cb\u003e3\u003c/b\u003e) showed good activity against both insect species. Additional two derivatives (\u003cb\u003e6\u003c/b\u003e and \u003cb\u003e9\u003c/b\u003e) were active against \u003cem\u003eM.domestica\u003c/em\u003e L. and the derivatives (\u003cb\u003e1\u003c/b\u003e\u0026ndash;\u003cb\u003e3\u003c/b\u003e, \u003cb\u003e8\u003c/b\u003e) were active against \u003cem\u003eCx\u003c/em\u003e. \u003cem\u003equinquefasciatus\u003c/em\u003e larvae.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e","manuscriptTitle":"Insecticidal activity of isoborneol derivatives against Musca domestica adults and Culex quinquefasciatus larvae","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-19 14:49:11","doi":"10.21203/rs.3.rs-3839460/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major Revision","date":"2024-06-29T12:44:02+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2024-03-20T11:02:53+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-03-15T14:31:50+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"Environmental Science and Pollution Research","date":"2024-02-21T16:57:26+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-02-06T04:30:08+00:00","index":"","fulltext":""},{"type":"submitted","content":"Environmental Science and Pollution Research","date":"2024-01-29T03:35:14+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"environmental-science-and-pollution-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"espr","sideBox":"Learn more about [Environmental Science and Pollution Research](https://www.springer.com/journal/11356)","snPcode":"11356","submissionUrl":"https://submission.nature.com/new-submission/11356/3","title":"Environmental Science and Pollution Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"47e6ddeb-9d0c-41ed-8af5-e358de01f7c3","owner":[],"postedDate":"March 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-08-26T16:06:27+00:00","versionOfRecord":{"articleIdentity":"rs-3839460","link":"https://doi.org/10.1007/s11356-024-34719-3","journal":{"identity":"environmental-science-and-pollution-research","isVorOnly":false,"title":"Environmental Science and Pollution Research"},"publishedOn":"2024-08-23 15:58:06","publishedOnDateReadable":"August 23rd, 2024"},"versionCreatedAt":"2024-03-19 14:49:11","video":"","vorDoi":"10.1007/s11356-024-34719-3","vorDoiUrl":"https://doi.org/10.1007/s11356-024-34719-3","workflowStages":[]},"version":"v1","identity":"rs-3839460","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3839460","identity":"rs-3839460","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}