Antibacterial Activities of Depsidones from Timorese Endophytic Fungus Corynespora cassiicola against Methicilin and Multidrug-Resistant Bacteria

Antibacterial Activities of Depsidones from Timorese Endophytic Fungus Corynespora cassiicola against Methicilin and Multidrug-Resistant Bacteria | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Short Report Antibacterial Activities of Depsidones from Timorese Endophytic Fungus Corynespora cassiicola against Methicilin and Multidrug-Resistant Bacteria Antonius R. B. Ola, Suwari Suwari, Dodi Darmakusuma, Luther Kadang, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8933048/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 4 You are reading this latest preprint version Abstract Chemical investigation of the screened active extract from fungal endophyte Corynespora cassicola associated with medicinal plants Anonna squamosa collected in Timor Island (Indonesia) led to the isolation of four depsidone compounds corynesidone A ( 1 ), B ( 2 ), C ( 3 ) and D ( 4 ). The individual compound was tested for their antibacterial property against multi drug resistant bacteria and for their cytotoxic activity against murine lymphoma (L5178Y) cell line. While compound 1–4 were inactive in the cytotoxic assay, they displayed antibacterial potency toward multi drug resistant clinical isolates Staphylococcus aureus 25697 (MRSA) with MIC value of 16–64 µ g/mL. Moreover, compound 3 was found to be active against Streptococcus pneumonia with MIC value of 32 µ g/mL. Anonna squamosa Antibacterial Cytotoxic corrynesidone Corrynespora cassiicola Endophytic fungus Figures Figure 1 Introduction The resistance of bacteria to the clinically used of antibiotics has brought serious consequences in terms of therapeutic failures due to the lower potency of antibiotic and impact on global public health care system around the world. Methicilin-resistant Staphylococcus aureus (MRSA) and multi-drug-resistant (MDR) variants of this species are the most important examples of the antibiotic-resistant pathogens which are spreading worldwide in hospitals as well as within the extended care facilities and the community [ 1 – 3 ]. They even have been reported to be resistant against antibiotics which were launched during the last decade such as linezolid and daptomycin [ 4 – 6 ]. Moreover, the World Health Organization have alarmed that these resistance situations have been closer to the post antibiotic age due the increasing number of therapy failure. Therefore, there is an urgent and immediate need to discover and develop new antibiotics against multi drug resistant bacteria. It has been well recorded that endophytic fungi that inhabit higher plants as commensals or symbionts are promising sources of antibacterial agents [ 7 , 8 ]. We have started the work on investigating the potential pharmacologically active metabolites from the endophytic fungi associated with the medicinal plants growing in tropical dry land around Timor Island, Indonesia. Dihydroanthracenones diaporthemins A and B were the first report of new pharmacologically active metabolites produced by the endophytic fungus Diaporthe melonis isolated from the leaves of Timorese medicinal plants Annona squamosa [ 9 ]. The other new natural products discovered from the fungus associated with Timorese Medicinal plants were arugosin J and xylarugosin produced by the fungus Xylaria sp from the leaves of medicinal plant Curcuma xanthorrhiza grown in Timor Island [ 10 ]. Out all the reported metabolites from the endophytic fungi isolated from Timorese medicinal plants, flavomannin-6,60-di-O-methyl ether was the most active antibacterial agents with IC 50 2 µg/mL against Streptococcus pneumoniae ATCC 49619 [ 9 ]. In this study, we report the antibiotic potential of corynesidones A, B, C and D from the Timorese endophytic fungi Corynespora cassicola associated with Annona squamosa against multi drug resistant bacteria Staphylococcus aureus and Enterococcus faecaelis together with the standard strain Streptococcus pneumonia . To the best of our knowledge, this is the first report of corynesidones compounds against the multi drug resistant bacteria. This study again confirmed that the intensive investigation of endophytes from Timorese medicinal plants will provide more bioactive molecules in the future for further development in pharmaceutical and medicines. Results and Discussion The fungus Corynespora cassicola was isolated from the leaves of Annona squamosa collected in Timor, Eastern Indonesia. The ethyl acetate extract from the culture of C. casiicola on solid rice medium was subjected to chromatographic separation on different stationary phases, including silica gel and Sephadex LH-20. Compounds 1 , 2 , 3 and 4 were elucidated based on their NMR (Table 1 ) and MS data together with the comparison of spectroscopic data from those in the literatures [ 11 – 14 ]. As part of our screening for pharmacologically active metabolites, corynesidones A ( 1 ), B ( 2 ), C ( 3 ) and D ( 4 ) was investigated for their antibacterial activity against a spectrum of Gram-positive species, including antibiotic-susc eptible reference strains ( Staphylococcus aureus ATCC 29213 and Streptococcus pneumoniae ATCC 49619) as well as multi-resistant clinical isolates ( Staphylococcus aureus 25697 and strain Enterococcus faecalis UW 2689). The Minimum Inhibitory Concentration (MIC) values were determined by broth microdilution assays (Table 2 ). Table 1 NMR Data of Corynesidone A (1), B (2), C (3) and D (4) No Corynesidone A a Corynesidone B a Corynesidone C a Corynesidone D b δH (J in Hz) δ 13 C δH (J in Hz) δ 13 C δH (J in Hz) δ 13 C δH (J in Hz) δ 13 C 1 145.1 128.1 129.4 144.5 2 6.66 (br s) 115.5 141.6 142.6 6.59 (d, 1.75) 115.5 3 162.4 149.3 150.4 162.9 4 6.66 (br s) 104.7 6.78 s 104.1 6.73 s 105.4 6.59 (d, 1.75) 104.5 4a 161.5 155.0 156.9 161.9 5a 142.1 142.8 144.2 139.5 6 131.3 133.5 132.3 132.9 7 6.53 (dd 2.8, 0.7) 113.5 110.0 6.52 d 2.1 114.6 115.5 8 154.5 160.3 155.6 162.6 9 6.52 (d 2.8) 104.9 6.64 s 106.3 6.52 d 2.1 106.2 6.36 s 104.9 9a 144.9 149.4 146.4 145.5 11 163.3 161.6 164.0 162.2 11a 112.8 112.9 114.6 112.7 12 2.39 s 20.21 2.31 s 12.51 2.35 s 14.1 2.33 s 20.50 13 2.37 s 15.00 2.70 s 14.10 2.33 s 16.4 2.70 s 13.90 14 172.0 171.5 a Measured in Aceton-d6 b Measured in DMSO Corynesidone A ( 1 ) was found to be the most active compound against the standard and the methicillin resistant strain of Staphylococcus aureus with MIC value 16 µ g/mL for both strains followed by corynesidone B and C with MIC value 32 µ g/mL (Table 2 ). This result was consistent with previous report of Corynesidone B that have moderate activity against standard strain S. aureus at the concentration 40 µ g/mL using agar diffusion method [ 14 ]. Corynesidone C showed the highest MIC value (32 µ g/mL) against the standard strain S. pneumonia followed by corynesidone B with MIC value of 64 µ g/mL while corynesidone A and D was inactive at the concentration 64 µ g/mL. It is interesting to note that corynesidone B and C displayed comparable activity to vancomycin with MIC value of 64 µ g/mL against vancomycin-resistant enterococci . From all the tested corynesidones, corynesidone D was the only corynesidone that was found to be inactive against all strain up to highest concentration tested of 64 µ g/mL. Table 2 Antibacterial Activity of Corynesidone A ( 1 ), B ( 2 ), C ( 3 ) and D ( 4 ) tested organism resistance phenotype a 1 2 3 4 Vancomycin Ciprofloxacin Tetracycline S. aureus ATCC 29213 susceptible 16 32 32 > 64 0.5 0.125 − 0.0625 0.25 S. aureus 25697 AMX R d , CHL R , CIP R , CLI R , ERY R , FOS R , GEN R , KAN R , NIT R , TET R , (MRSA e ) 16 32 32 > 64 0.5 8 32 S. pneumoniae ATCC 49619 susceptible > 64 64 32 > 63 0.125 0.25 0.0625 E. faecalis UW 2689 CLA R , ERY R , MXF R , TEL R , (VRE f ) - 64 64 - 64 16 64 a Antibiotic abbreviations and breakpoints for resistance were applied according to the CLSI guidelines 43 : AMX, amoxicillin; CHL, chloramphenicol; CIP, ciprofloxacin; CLA, clarithromycin; CLI, clindamycin; ERY, erythromycin; GEN, gentamycin; KAN, kanamycin; MXF, moxifloxacin; NIT, nitrofurantoin; TEL, telithromycin; TET, tetracycline. c The experiment was repeated six times and showed variations in the depicted ranges. d R: resistant. e MRSA: methicillinresistant S. aureus . f VRE: vancomycin-resistant enterococci.. Cytotoxic Activity The active corynesidone A, B, C and D were then tested for their cytotoxic activity against the murine lymphoma (L5178Y) cell line. All the tested corynesidones did not significantly inhibit the growth of the murine lymphoma cell (see Table 2 ) indicating that their antibacterial potency was not due to their toxicity effect. Structure Activity Relationship Corynesidone A and C seem to be more active compared to corynesidone B and D. This might be due to the absence of a free carboxylic acid moiety on activity. The presence of carboxylic acid moiety lead to the less lipophilic of compounds 2 and 4, thus possibly caused the minimal effect. This was in agreeement of the earlier reports regarding the antibacterial activity of lichen derived depsidones (15). It is noteworthy that multiresistant clinical isolates S. aureus was as susceptible as quality control strains for corynesidone A and B, the latter being recommended by the Clinical Laboratory Standards Institute (CLSI) [ 16 ] for sensitive antibiotic testing. Table 3 Cytotoxic Activity of Corynesidone A (1), B (2), C (3) and D (4) Compound Percent of Growth Inhibition (10 µ g/mL) Corynesidone A 45.5 Corynesidone B 8.8 Corynesidone C 28.2 Corynesidone D 5.5 Although corynesidone D ( 4 ) was inactive in the antibacterial testing, it is interesting to note that corynesidone D was found as the most active compound during cytotoxic assay followed by corynesidone B ( 2 ). This finding revealed that the antibacterial activity of 1 , 2 , 3 and 4 was not contributed by their cytototoxic activity. Moreover, this finding highlight that the carboxyl group of the corynesidones are important for the cytotoxic activity. Therefore, this finding lead to the possibility of development of selective antibacterial agent and selective cytotoxic agent from typical corynesidone metabolites. Conclusion In this study, we report for the first time the antibacterial properties of corynesidones against Methicilin and Multidrug-Resistant Bacteria. This study has demonstrated that the antibacterial activity of 1, 2, 3 and 4 was not contributed by their cytototoxic activity. Therefore, this finding leads to the possibility of development of selective antibacterial agents and selective cytotoxic agent from typical corynesidone metabolites. Declarations Acknowledgements This research was supported from Penelitian Pasca Doktor by Kementerian Riset, Pendidikan dan Teknologi No: 45/UN15.19/LT/2019, DIPA Universitas Nusa Cendana No 16/ UN15.15.3.PPK/SPP/FST/IV/2023 dan Penelitian Guru Besar 329/UN15.22/LT/2024. Author contributions All authors read and approved the final manuscript. Data availability All correspond data are within the manuscript and its Additional files. Competing interests The authors declare no conflict of interest. References Bassetti S, Tschudin-Sutter S, Egli A, Osthoff M (2022) Optimizing antibiotic therapies to reduce the risk of bacterial resistance. Eur J Intern Med 99:7–12 Mancuso G, Midiri A, Gerace E, Biondo C (2021) Bacterial Antibiotic Resistance: The Most Critical Pathogens. Pathogens 10(10):1310 Oliveira DMPD, Forde BM, Kidd TJ, Harris PNA, Schembri MA, Beatson SA (2020) Antimicrobial Resistance in ESKAPE Pathogens. Clin Microbiol Rev 33(3). 10.1128/cmr.00181 – 19 Sharland M, Gandra S, Huttner B, Moja L, Pulcini C, Zeng M, Mendelson M, Cappello B, Cooke G, Magrini N (2019) Encouraging AWaRe-ness and discouraging inappropriate antibiotic use—the new 2019 Essential Medicines List becomes a global antibiotic stewardship tool. Lancet Infect Dis 19(12):1278–1280 Bæk KT, Thøgersen L, Mogenssen RG, Mellergaard M, Thomsen LE, Petersen A, Skov S, Cameron DR, Peleg AY, Free D (2015) Stepwise Decrease in Daptomycin Susceptibility in Clinical Staphylococcus aureus Isolates Associated with with an initial mutation in rpoB and a compensatory inactivation of the clpX gene. Antimicrob Agents Chemother 59(11):6983–6991 Chen C-J, Huang Y-C, Shie S-S (2020) Evolution of Multi-Resistance to Vancomycin, Daptomycin, and Linezolid in Methicillin-Resistant Staphylococcus aureus Causing Persistent Bacteremia. Front microbiol. ;11 Ola ARB, Darmakusuma D, Kadang L, Karyawati AT, Ledoh SMF, Gauru I, Ola PD, Suwari, Belli HLL (2022) Bioactive Secondary Metabolites from the Endophytic Fungi Alternaria sp. Indones. J. Chem. 2022;22(4):7 Ola ARB, Lapailaka T, Wogo HE, Henuk JBD, Simamora A, Mukkun L, Proskch P, Pham CD (2021) Bioactive Secondary Metabolites from the Mangrove Endophytic Fungi Nigrospora oryzae. Indones J Chem 21(4):7 Ola ARB, Debbab A, Kurtán T, Brötz-Oesterhelt H, Aly AH, Proksch P (2014) Dihydroanthracenone metabolites from the endophytic fungus Diaporthe melonis isolated from Annona squamosa. Tetrahedron Lett 55(20):3147–3150 Hammerschmidt L, Ola A, Müller WEG, Lin W, Mándi A, Kurtán T, Proksch P, Ali AH (2015) Two new metabolites from the endophytic fungus Xylaria sp. isolated from the medicinal plant Curcuma xanthorrhiza. Tetrahedron Lett 56(10):1193–1197 Chomcheon P, Wiyakrutta S, Sriubolmas N, Ngamrojanavanich N, Kengtong S, Mahidol C (2009) Aromatase inhibitory, radical scavenging, and antioxidant activities of depsidones and diaryl ethers from the endophytic fungus Corynespora cassiicola L36. Phytochem 70(3):407–413 Okoye FBC, Lu S, Nworu CS, Esimone CO, Proksch P, Chadli A, Debbab A (2013) Depsidone and diaryl ether derivatives from the fungus Corynespora cassiicola, an endophyte of Gongronema latifolium. Tetrahedron Lett 54(32):4210–4214 Ebrahim W, Aly AH, Mándi A, Totzke F, Kubbutat MHG, Wray V, Wen-Han L, Haofu D, Peter Proksch P, Kurtán T, Debbab A (2012) Decalactone Derivatives from Corynespora cassiicola, an Endophytic Fungus of the Mangrove Plant Laguncularia racemosa. Eur J Org Chem 2012(18):3476–3484 Talontsi FM, Douanla-Meli C, Laatsch H (2013) Depsidones from an Endophytic Fungus Chaetomium sp. Associated with Zanthoxylum leprieurii. Z Naturforsch B 68(11):1259–1264 Kokubun T, Shiu WKP, Gibbons S (2007) Inhibitory Activities of Lichen-Derived Compounds against Methicillin- and Multidrug-Resistant Staphylococcus aureus. Planta Med 73(02):176–179 CLSI. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically (2012) Approved Standart – Ninth Edition. CLSI document M07-A9. Clinical and Laboratory Standarts Institute, Wayne, PA Additional Declarations No competing interests reported. Supplementary Files SupportinginformatiOnCorynesporacassiicola.docx Supplementary data including experimental part and compound identification, together with HPLC chromatograms, UV and LC-MS spectra and NMR spectra of 1-4 associated with this article can be found in the online version, at http://XXXXXXXXXXXXXX Additional file 1. Supplementary data. Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 17 Mar, 2026 Editor assigned by journal 25 Feb, 2026 Submission checks completed at journal 23 Feb, 2026 First submitted to journal 21 Feb, 2026 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-8933048","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":607846698,"identity":"f9181618-6ffd-4173-8574-0cfd6ae25208","order_by":0,"name":"Antonius R. B. 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Supplementary data.\u003c/p\u003e","description":"","filename":"SupportinginformatiOnCorynesporacassiicola.docx","url":"https://assets-eu.researchsquare.com/files/rs-8933048/v1/451468483a28038cd8156471.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Antibacterial Activities of Depsidones from Timorese Endophytic Fungus Corynespora cassiicola against Methicilin and Multidrug-Resistant Bacteria","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe resistance of bacteria to the clinically used of antibiotics has brought serious consequences in terms of therapeutic failures due to the lower potency of antibiotic and impact on global public health care system around the world. Methicilin-resistant \u003cem\u003eStaphylococcus aureus\u003c/em\u003e (MRSA) and multi-drug-resistant (MDR) variants of this species are the most important examples of the antibiotic-resistant pathogens which are spreading worldwide in hospitals as well as within the extended care facilities and the community [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. They even have been reported to be resistant against antibiotics which were launched during the last decade such as linezolid and daptomycin [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Moreover, the World Health Organization have alarmed that these resistance situations have been closer to the post antibiotic age due the increasing number of therapy failure. Therefore, there is an urgent and immediate need to discover and develop new antibiotics against multi drug resistant bacteria.\u003c/p\u003e \u003cp\u003eIt has been well recorded that endophytic fungi that inhabit higher plants as commensals or symbionts are promising sources of antibacterial agents [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. We have started the work on investigating the potential pharmacologically active metabolites from the endophytic fungi associated with the medicinal plants growing in tropical dry land around Timor Island, Indonesia. Dihydroanthracenones diaporthemins A and B were the first report of new pharmacologically active metabolites produced by the endophytic fungus \u003cem\u003eDiaporthe melonis\u003c/em\u003e isolated from the leaves of Timorese medicinal plants \u003cem\u003eAnnona squamosa\u003c/em\u003e [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The other new natural products discovered from the fungus associated with Timorese Medicinal plants were arugosin J and xylarugosin produced by the fungus \u003cem\u003eXylaria sp\u003c/em\u003e from the leaves of medicinal plant \u003cem\u003eCurcuma xanthorrhiza\u003c/em\u003e grown in Timor Island [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Out all the reported metabolites from the endophytic fungi isolated from Timorese medicinal plants, flavomannin-6,60-di-O-methyl ether was the most active antibacterial agents with IC\u003csub\u003e50\u003c/sub\u003e 2 \u0026micro;g/mL against \u003cem\u003eStreptococcus pneumoniae\u003c/em\u003e ATCC 49619 [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this study, we report the antibiotic potential of corynesidones A, B, C and D from the Timorese endophytic fungi \u003cem\u003eCorynespora cassicola\u003c/em\u003e associated with \u003cem\u003eAnnona squamosa\u003c/em\u003e against multi drug resistant bacteria \u003cem\u003eStaphylococcus aureus\u003c/em\u003e and \u003cem\u003eEnterococcus faecaelis\u003c/em\u003e together with the standard strain \u003cem\u003eStreptococcus pneumonia\u003c/em\u003e. To the best of our knowledge, this is the first report of corynesidones compounds against the multi drug resistant bacteria. This study again confirmed that the intensive investigation of endophytes from Timorese medicinal plants will provide more bioactive molecules in the future for further development in pharmaceutical and medicines.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Results and Discussion","content":"\u003cp\u003eThe fungus \u003cem\u003eCorynespora cassicola\u003c/em\u003e was isolated from the leaves of \u003cem\u003eAnnona squamosa\u003c/em\u003e collected in Timor, Eastern Indonesia. The ethyl acetate extract from the culture of \u003cem\u003eC. casiicola\u003c/em\u003e on solid rice medium was subjected to chromatographic separation on different stationary phases, including silica gel and Sephadex LH-20. Compounds \u003cb\u003e1\u003c/b\u003e, \u003cb\u003e2\u003c/b\u003e, \u003cb\u003e3\u003c/b\u003e and \u003cb\u003e4\u003c/b\u003e were elucidated based on their NMR (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) and MS data together with the comparison of spectroscopic data from those in the literatures [\u003cspan additionalcitationids=\"CR12 CR13\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAs part of our screening for pharmacologically active metabolites, corynesidones A (\u003cb\u003e1\u003c/b\u003e), B (\u003cb\u003e2\u003c/b\u003e), C (\u003cb\u003e3\u003c/b\u003e) and D (\u003cb\u003e4\u003c/b\u003e) was investigated for their antibacterial activity against a spectrum of Gram-positive species, including antibiotic-susc eptible reference strains (\u003cem\u003eStaphylococcus aureus\u003c/em\u003e ATCC 29213 and \u003cem\u003eStreptococcus pneumoniae\u003c/em\u003e ATCC 49619) as well as multi-resistant clinical isolates (\u003cem\u003eStaphylococcus aureus\u003c/em\u003e 25697 and strain \u003cem\u003eEnterococcus faecalis\u003c/em\u003e UW 2689). The Minimum Inhibitory Concentration (MIC) values were determined by broth microdilution assays (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\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\u003eNMR Data of Corynesidone A (1), B (2), C (3) and D (4)\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=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" 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=\"left\" 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\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCorynesidone A\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eCorynesidone B\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eCorynesidone C\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eCorynesidone D\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eδH (J in Hz)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eδ \u003csup\u003e13\u003c/sup\u003eC\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eδH (J in Hz)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eδ \u003csup\u003e13\u003c/sup\u003eC\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eδH (J in Hz)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eδ \u003csup\u003e13\u003c/sup\u003eC\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eδH (J in Hz)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eδ \u003csup\u003e13\u003c/sup\u003eC\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=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e145.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e128.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e129.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e144.5\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=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.66 (br s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e115.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e141.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e142.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e6.59 (d, 1.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e115.5\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=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e162.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e149.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e150.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e162.9\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=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.66 (br s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e104.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.78 s\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e104.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.73 s\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e105.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e6.59 (d, 1.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e104.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e161.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e155.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e156.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e161.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e142.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e142.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e144.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e139.5\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=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e131.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e133.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e132.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e132.9\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=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.53 (dd 2.8, 0.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e113.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e110.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.52 d 2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e114.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e115.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e154.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e160.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e155.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e162.6\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=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.52 (d 2.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e104.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.64 s\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e106.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.52 d 2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e106.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e6.36 s\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e104.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e144.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e149.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e146.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e145.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e163.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e161.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e164.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e162.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e112.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e112.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e114.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e112.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.39 s\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e20.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.31 s\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e12.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.35 s\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e14.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.33 s\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e20.50\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.37 s\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e15.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.70 s\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e14.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.33 s\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e16.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.70 s\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e13.90\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e172.0\u003c/p\u003e \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=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e171.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003e\u003csup\u003ea\u003c/sup\u003eMeasured in Aceton-d6 \u003csup\u003eb\u003c/sup\u003eMeasured in DMSO\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eCorynesidone A (\u003cb\u003e1\u003c/b\u003e) was found to be the most active compound against the standard and the methicillin resistant strain of \u003cem\u003eStaphylococcus aureus\u003c/em\u003e with MIC value 16\u003cem\u003e\u0026micro;\u003c/em\u003eg/mL for both strains followed by corynesidone B and C with MIC value 32 \u003cem\u003e\u0026micro;\u003c/em\u003eg/mL (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). This result was consistent with previous report of Corynesidone B that have moderate activity against standard strain \u003cem\u003eS. aureus\u003c/em\u003e at the concentration 40 \u003cem\u003e\u0026micro;\u003c/em\u003eg/mL using agar diffusion method [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCorynesidone C showed the highest MIC value (32 \u003cem\u003e\u0026micro;\u003c/em\u003eg/mL) against the standard strain \u003cem\u003eS. pneumonia\u003c/em\u003e followed by corynesidone B with MIC value of 64 \u003cem\u003e\u0026micro;\u003c/em\u003eg/mL while corynesidone A and D was inactive at the concentration 64 \u003cem\u003e\u0026micro;\u003c/em\u003eg/mL. It is interesting to note that corynesidone B and C displayed comparable activity to vancomycin with MIC value of 64 \u003cem\u003e\u0026micro;\u003c/em\u003eg/mL against vancomycin-resistant \u003cem\u003eenterococci\u003c/em\u003e. From all the tested corynesidones, corynesidone D was the only corynesidone that was found to be inactive against all strain up to highest concentration tested of 64 \u003cem\u003e\u0026micro;\u003c/em\u003eg/mL.\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\u003eAntibacterial Activity of Corynesidone A (\u003cb\u003e1\u003c/b\u003e), B (\u003cb\u003e2\u003c/b\u003e), C (\u003cb\u003e3\u003c/b\u003e) and D (\u003cb\u003e4\u003c/b\u003e)\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=\"left\" 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=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003etested organism\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eresistance phenotype\u003csup\u003e\u003cem\u003ea\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eVancomycin\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eCiprofloxacin\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eTetracycline\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eS. aureus\u003c/em\u003e ATCC 29213\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003esusceptible\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.125\u0026thinsp;\u0026minus;\u0026thinsp;0.0625\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eS. aureus\u003c/em\u003e 25697\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAMX\u003csup\u003eR\u003cem\u003ed\u003c/em\u003e\u003c/sup\u003e, CHL\u003csup\u003eR\u003c/sup\u003e, CIP\u003csup\u003eR\u003c/sup\u003e, CLI\u003csup\u003eR\u003c/sup\u003e, ERY\u003csup\u003eR\u003c/sup\u003e, FOS\u003csup\u003eR\u003c/sup\u003e, GEN\u003csup\u003eR\u003c/sup\u003e, KAN\u003csup\u003eR\u003c/sup\u003e, NIT\u003csup\u003eR\u003c/sup\u003e, TET\u003csup\u003eR\u003c/sup\u003e, (MRSA\u003csup\u003e\u003cem\u003ee\u003c/em\u003e\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eS. pneumoniae\u003c/em\u003e ATCC 49619\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003esusceptible\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.125\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.0625\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eE. faecalis\u003c/em\u003e UW 2689\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCLA\u003csup\u003eR\u003c/sup\u003e, ERY\u003csup\u003eR\u003c/sup\u003e, MXF\u003csup\u003eR\u003c/sup\u003e, TEL\u003csup\u003eR\u003c/sup\u003e, (VRE\u003csup\u003e\u003cem\u003ef\u003c/em\u003e\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e64\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003csup\u003e \u003cem\u003ea\u003c/em\u003e \u003c/sup\u003e Antibiotic abbreviations and breakpoints for resistance were applied according to the CLSI guidelines\u003csup\u003e43\u003c/sup\u003e: AMX, amoxicillin; CHL, chloramphenicol; CIP, ciprofloxacin; CLA, clarithromycin; CLI, clindamycin; ERY, erythromycin; GEN, gentamycin; KAN, kanamycin; MXF, moxifloxacin; NIT, nitrofurantoin; TEL, telithromycin; TET, tetracycline. \u003csup\u003e\u003cem\u003ec\u003c/em\u003e\u003c/sup\u003eThe experiment was repeated six times and showed variations in the depicted ranges. \u003csup\u003e\u003cem\u003ed\u003c/em\u003e\u003c/sup\u003e R: resistant. \u003csup\u003e\u003cem\u003ee\u003c/em\u003e\u003c/sup\u003e MRSA: methicillinresistant \u003cem\u003eS. aureus\u003c/em\u003e. \u003csup\u003e\u003cem\u003ef\u003c/em\u003e\u003c/sup\u003e VRE: vancomycin-resistant enterococci..\u003c/p\u003e \u003cp\u003eCytotoxic Activity\u003c/p\u003e \u003cp\u003eThe active corynesidone A, B, C and D were then tested for their cytotoxic activity against the murine lymphoma (L5178Y) cell line. All the tested corynesidones did not significantly inhibit the growth of the murine lymphoma cell (see Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) indicating that their antibacterial potency was not due to their toxicity effect.\u003c/p\u003e \u003cp\u003eStructure Activity Relationship\u003c/p\u003e \u003cp\u003eCorynesidone A and C seem to be more active compared to corynesidone B and D. This might be due to the absence of a free carboxylic acid moiety on activity. The presence of carboxylic acid moiety lead to the less lipophilic of compounds 2 and 4, thus possibly caused the minimal effect. This was in agreeement of the earlier reports regarding the antibacterial activity of lichen derived depsidones (15). It is noteworthy that multiresistant clinical isolates \u003cem\u003eS. aureus\u003c/em\u003e was as susceptible as quality control strains for corynesidone A and B, the latter being recommended by the Clinical Laboratory Standards Institute (CLSI) [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] for sensitive antibiotic testing.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCytotoxic Activity of Corynesidone A (1), B (2), C (3) and D (4)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCompound\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePercent of Growth Inhibition (10 \u003cem\u003e\u0026micro;\u003c/em\u003eg/mL)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCorynesidone A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e45.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCorynesidone B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCorynesidone C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e28.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCorynesidone D\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAlthough corynesidone D (\u003cb\u003e4\u003c/b\u003e) was inactive in the antibacterial testing, it is interesting to note that corynesidone D was found as the most active compound during cytotoxic assay followed by corynesidone B (\u003cb\u003e2\u003c/b\u003e). This finding revealed that the antibacterial activity of \u003cb\u003e1\u003c/b\u003e, \u003cb\u003e2\u003c/b\u003e, \u003cb\u003e3\u003c/b\u003e and \u003cb\u003e4\u003c/b\u003e was not contributed by their cytototoxic activity. Moreover, this finding highlight that the carboxyl group of the corynesidones are important for the cytotoxic activity. Therefore, this finding lead to the possibility of development of selective antibacterial agent and selective cytotoxic agent from typical corynesidone metabolites.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn this study, we report for the first time the antibacterial properties of corynesidones against Methicilin and Multidrug-Resistant Bacteria. This study has demonstrated that the antibacterial activity of 1, 2, 3 and 4 was not contributed by their cytototoxic activity. Therefore, this finding leads to the possibility of development of selective antibacterial agents and selective cytotoxic agent from typical corynesidone metabolites.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was supported from Penelitian Pasca Doktor by Kementerian Riset, Pendidikan dan Teknologi No: \u0026nbsp;45/UN15.19/LT/2019, DIPA Universitas Nusa Cendana No 16/ \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;UN15.15.3.PPK/SPP/FST/IV/2023 dan Penelitian Guru Besar 329/UN15.22/LT/2024.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll correspond data are within the manuscript and its Additional files.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBassetti S, Tschudin-Sutter S, Egli A, Osthoff M (2022) Optimizing antibiotic therapies to reduce the risk of bacterial resistance. 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Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically (2012) Approved Standart \u0026ndash; Ninth Edition. CLSI document M07-A9. Clinical and Laboratory Standarts Institute, Wayne, PA\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":false,"email":"","identity":"current-microbiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Current Microbiology","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"VoR Journals","inReviewEnabled":false,"inReviewRevisionsEnabled":false},"keywords":"Anonna squamosa, Antibacterial, Cytotoxic, corrynesidone, Corrynespora cassiicola, Endophytic fungus","lastPublishedDoi":"10.21203/rs.3.rs-8933048/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8933048/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eChemical investigation of the screened active extract from fungal endophyte \u003cem\u003eCorynespora cassicola\u003c/em\u003e associated with medicinal plants \u003cem\u003eAnonna squamosa\u003c/em\u003e collected in Timor Island (Indonesia) led to the isolation of four depsidone compounds corynesidone A (\u003cb\u003e1\u003c/b\u003e), B (\u003cb\u003e2\u003c/b\u003e), C (\u003cb\u003e3\u003c/b\u003e) and D (\u003cb\u003e4\u003c/b\u003e). The individual compound was tested for their antibacterial property against multi drug resistant bacteria and for their cytotoxic activity against murine lymphoma (L5178Y) cell line. While compound \u003cb\u003e1\u0026ndash;4\u003c/b\u003e were inactive in the cytotoxic assay, they displayed antibacterial potency toward multi drug resistant clinical isolates \u003cem\u003eStaphylococcus aureus\u003c/em\u003e 25697 (MRSA) with MIC value of 16\u0026ndash;64 \u003cem\u003e\u0026micro;\u003c/em\u003eg/mL. Moreover, compound \u003cb\u003e3\u003c/b\u003e was found to be active against \u003cem\u003eStreptococcus pneumonia\u003c/em\u003e with MIC value of 32 \u003cem\u003e\u0026micro;\u003c/em\u003eg/mL.\u003c/p\u003e","manuscriptTitle":"Antibacterial Activities of Depsidones from Timorese Endophytic Fungus Corynespora cassiicola against Methicilin and Multidrug-Resistant Bacteria","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-13 16:25:50","doi":"10.21203/rs.3.rs-8933048/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-03-17T20:49:24+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-25T20:51:23+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-23T05:53:40+00:00","index":"","fulltext":""},{"type":"submitted","content":"Current Microbiology","date":"2026-02-21T11:19:45+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":false,"email":"","identity":"current-microbiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Current Microbiology","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"VoR Journals","inReviewEnabled":false,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"8c45dc40-a8fe-4807-a16f-07d894e9d48b","owner":[],"postedDate":"April 13th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-04-23T19:54:03+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-13 16:25:50","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8933048","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8933048","identity":"rs-8933048","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}