Antimicrobial and Antidermatophytic Dihydroisocoumarins and Picolinic Acids Produced by Endophytic Fungus Fusarium napiforme of Faurea saligna Harv.
Abstract
Fungal metabolites are reservoirs of bioactive molecules that impart therapeutic potential to medicinal plants. The fungus Fusarium napiforme was isolated from the internal tissues of the leaves of Faurea saligna. In this study, four dihydroisocoumarin: 7-butyl-15-enyl-6,8-dihydroxy-3(R)-pent-9,11-dienylisochroman-1-one (1), 7-butyl-15-enyl-6,8-dihydroxy-3(R)-pent-11-enylisochroman-1-one (2), 7-butyl-6,8-dihydroxy-3(R)-pent-11-enylisochroman-1-one (3), 7-butyl-6,8-dihydroxy-3(R)-pentylisochroman-1-one (4) and two piclinic acid derivatives: dehydrofusaric acid (5) and fusaric acid (6) were isolated from endophytic fungus F. napiforme. The elucidation of the chemical structures of the isolated compounds was performed by analysis based on spectroscopic analysis and comparison with reported literature. Compounds 1-6 were tested for antimicrobial and antidermatophytic activity against selected bacteria and fungi. All the compounds exhibited selective antibacterial activity against Staphylococcus aureus and Escherichia coli with a minimum inhibitory concentration (MIC) range of 62 – 175 µg/mL. Compounds 5 and 6 further exhibited antibacterial activity against Klepsiella pneumoniae with MIC value of 150 µg/mL. None of the compounds showed activity against Pseudomonas aeruginosa. Furthermore, all the compounds exhibited antifungal activity against Candida albicans with MIC values ranging from 48 µg/mL to 150 µg/mL. Compounds 1-4 further exhibited antidermatophytic activity against Trichophyton rubrum, Trichophyton benhamiae and Trichophyton interdigitale, with minimum inhibitory concentration (MIC) values ranging from 33.3 µg/mL to 66.6 µg/mL. Compounds 5 and 6 did not show any antidermatophytic activity against the highest concentration of 66.6 µg/mLused. Although, these compounds have been previously identified, this is the first instance of their reporting in endophytic fungi F. napiforme isolated from F, saligna. These results provide promising baseline information for the potential use of the compounds of this endophytic fungi as an antimicrobial and antidermatophytic for the control of diseases.
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Ahmed, A. M., Mahmoud, B. K., Millán-Aguiñaga, N., Abdelmohsen, U. R., & Fouad, M. A. (2023). The endophytic Fusarium strains: a treasure trove of natural products. RSC advances, 13(2), 1339-1369.
Alejo-Armijo, A., Cobo, A., Alejo-Armijo, A., Altarejos, J., Salido, S., & Ortega-Morente, E. (2025). Evaluation of antibacterial and antibiofilm properties of phenolics with coumarin, naphthoquinone and pyranone moieties against foodborne microorganisms. Molecules, 30(4), 944.
Amuka, O., Machocho, A., Okemo, P., & Mbugua, P. (2015). Antifungal and antibacterial activity of crude stem bark extracts' of Bersama abysinicca Verdc. and Faurea saligna Harr. Research Journal of Medicinal Plant 9 (4), 160-169.
Arumugam, T., Ghazi, T., Abdul, N. S., & Chuturgoon, A. A. (2021). A review on the oxidative effects of the fusariotoxins: Fumonisin B1 and fusaric acid. Toxicology, 19, 181-190.
Boonman, N., Prachya, S., Boonmee, A., Kittakoop, P., Wiyakrutta, S., Sriubolmas, N. Warit S. & Chusattayanond, A. D.-a. (2012). In vitro acanthamoebicidal activity of fusaric acid and dehydrofusaric acid from an endophytic fungus Fusarium sp. Tlau3. Planta Medica, 78(14), 1562-1567.
Braca, A., Bader, A., & De Tommasi, N. (2012). Plant and fungi 3, 4-Dihydroisocoumarins: structures, biological activity, and taxonomic relationships. Studies in Natural Products Chemistry, 37, 191-215.
Capasso, R., Evidente, A., Cutignano, A., Vurro, M., Zonno, M. C., & Bottalico, A. (1996). Fusaric and 9, 10-dehydrofusaric acids and their methyl esters from Fusarium nygamai. Phytochemistry, 41(4), 1035-1039.
Chen, L., Li, C., Li, F., Chen, Z., Fang, R., Chen, Y., Zhu H. & Ju, J. (2026). Picolinic Acid Derivatives and Biosynthetic Pathway from Epicoccum sorghinum SDU-F549. Journal of Natural Products 89 (1), 329-335. .
Chen, M., Wang, R., Zhao, W., Yu, L., Zhang, C., Chang, S., Li Y., Zhang T., Xing J & Gan, M. (2019). Isocoumarindole A, a chlorinated isocoumarin and indole alkaloid hybrid metabolite from an endolichenic fungus Aspergillus sp. Organic Letters, 21(5), 1530-1533.
Chimponda, T., & Mukanganyama, S. (2010). Antimycobacterial activities of selected medicinal plants from Zimbabwe against Mycobacterium aurum and Corynebacterium glutamicum. Tropical Biomedicine, 27(3), 595-610.
Clay, K., & Schardl, C. (2002). Evolutionary origins and ecological consequences of endophyte symbiosis with grasses. The American Naturalist, 160(S4), S99-S127.
Devienne, K. F., Raddi, M. G., Coelho, R. G., & Vilegas, W. (2005). Structure–antimicrobial activity of some natural isocoumarins and their analogues. Phytomedicine, 12(5), 378-381.
Hamill, F., Apio, S., Mubiru, N., Bukenya-Ziraba, R., Mosango, M., Maganyi, O., & Soejarto, D. (2003). Traditional herbal drugs of Southern Uganda, II: literature analysis and antimicrobial assays. Journal of Ethnopharmacology, 84(1), 57-78. https://doi.org/https://doi.org/10.1016/S0378-8741(02)00289-1
Hoque, N., Afroz, F., Khatun, F., Rony, S. R., Hasan, C. M., Rana, M. S., & Sohrab, M. H. (2022). Physicochemical, pharmacokinetic and cytotoxicity of the compounds isolated from an endophyte Fusarium oxysporum: In vitro and in silico approaches. Toxins, 14(3), 159.
Huang, B. B., Liu, Y. Y., Zhu, P. F., Jiang, Y. C., & Ouyang, M.-A. (2020). Concise total synthesis and antifungal activities of fusaric acid, a natural product. Molecules, 25(17), 3859.
Hussain, H., & Green, I. R. (2017). A patent review of two fruitful decades (1997-2016) of Isocoumarin research. Expert opinion on therapeutic patents, 27(11), 1267-1275.
Ibrahim, S. R., Mohamed, S. G., Alsaadi, B. H., Althubyani, M. M., Awari, Z. I., Hussein, H. G., Aljohani A. A., Albasri J. F., Faraj S.A. & Mohamed, G. A. (2023). Secondary metabolites, biological activities, and industrial and biotechnological importance of Aspergillus sydowii. Marine Drugs, 21(8), 441.
Ji, Q., Ge, Z., Ge, Z., Chen, K., Wu, H., Liu, X., Huang, Y., Yuan, L., & Liao, F. (2016). Synthesis and biological evaluation of novel phosphoramidate derivatives of coumarin as chitin synthase inhibitors and antifungal agents. European Journal of Medicinal Chemistry, 108, 166-176.
Kayser, O., & Kolodziej, H. (1999). Antibacterial activity of simple coumarins: structural requirements for biological activity. Zeitschrift fur Naturforschung C, 54(12), 169-174.
Kellogg, J. J., & Raja, H. A. (2017). Endolichenic fungi: a new source of rich bioactive secondary metabolites on the horizon. Phytochemistry Reviews, 16(2), 271-293.
Kim, J. W., Ryu, J., & Shim, S. H. (2018). Chemical investigation on an endophytic fungus Gibberella moniliformis JS1055 derived from a halophyte Vitex rotundifolia. Natural Product Sciences, 24(3), 189-193.
Kolarczyková, D., Lysková, P., Švarcová, M., Kuklová, I., Dobiáš, R., Mallátová, N., Kolarik M., & Hubka, V. (2024). Terbinafine resistance in Trichophyton mentagrophytes and Trichophyton rubrum in the Czech Republic: A prospective multicentric study. Mycoses, 67(2), e13708.
Kola?ík, M., Vrublevskaya, M., Kajzrová, S., Kulišová, M., & Kolouchová, I. J. (2023). Taxonomic analysis reveals host preference of rare fungi in endophytes of Vitis vinifera from the Czech Republic. Folia Microbiologica, 68(6), 961-975.
Kongsaeree, P., Prabpai, S., Sriubolmas, N., Vongvein, C., & Wiyakrutta, S. (2003). Antimalarial dihydroisocoumarins produced by Geotrichum sp., an endophytic fungus of Crassocephalum c repidioides. Journal of Natural Products, 66(5), 709-711.
Kumar, J. S., Thirupataiah, B., Medishetti, R., Ray, A., Bele, S. D., Hossain, K. A., Reddy, G. S., Edwin, R. K., Hossain A. K., Joseph, A., Kumar, N., Shenoy G. G., Rao M. C., & Pal M., (2020). Rosuvastatin based novel 3-substituted isocoumarins/3-alkylidenephthalides: Ultrasound assisted synthesis and identification of new anticancer agents. European Journal of Medicinal Chemistry, 201, 112335.
Lawal, F., Bapela, M. J., Adebayo, S. A., Nkadimeng, S. M., Yusuf, A. A., Malterud, K. E., McGaw L. J., & Tshikalange, T. E. (2019). Anti-inflammatory potential of South African medicinal plants used for the treatment of sexually transmitted infections. South African Journal of Botany, 125, 62-71. https://doi.org/https://doi.org/10.1016/j.sajb.2019.06.023
Li-jian, X., Pei-qin, L., & Jiang-WZ, T. (2010). Two antimicrobial compounds fusaric acid and 9, 10-dehydrofusaric acid from endophytic Fusarium redolens Dzf2. Natural Product Research and Development, 22, 564-567.
Li, C., Zuo, C., Deng, G., Kuang, R., Yang, Q., Hu, C., Sheng O., Zhang S., Ma L., Wei, Y. & Yang J. (2013). Contamination of bananas with beauvericin and fusaric acid produced by Fusarium oxysporum f. sp. cubense. PloS one, 8(7), e70226.
Li, M., Yu, R., Bai, X., Wang, H., & Zhang, H. (2020). Fusarium: a treasure trove of bioactive secondary metabolites. Natural Product Reports, 37(12), 1568-1588.
Li, X., Wu, Y., & Liu, Z. (2021). Antifungal activity of an endophytic fungus Aspergillus versicolor DYSJ3 from Aphanamixis grandifolia Blume against Colletotrichum musae. Mycobiology, 49(5), 498-506.
Liu, D., Luo, Y., Zhang, C., Zhang, T., Guo, C., Wang, F., Zhanh, J., & Luo, D. (2026). Two new phytotoxic fusaric acid derivatives from the fungus Fusarium hechiense RH-A63. Phytochemistry Letters, 73, 104141.
Liu, S., Dai, H., Orfali, R. S., Lin, W., Liu, Z., & Proksch, P. (2016). New fusaric acid derivatives from the endophytic fungus Fusarium oxysporum and their phytotoxicity to barley leaves. Journal of Agricultural and Food Chemistry, 64(16), 3127-3132.
Lon?ar, M., Gašo-Soka?, D., & Molnar, M. (2023). Coumarin derivatives as antifungal agents--A review. Czech Journal of Food Sciences, 41(2), 79-91.
Oliveras, P., & Villanueva-Silva, R. (2025). Disruption of cell wall and membrane integrity as antioomycete and antifungal mode of action by fusaric and 9, 10-dehydrofusaric acids from endophytic fungus Fusarium lactis strain SME13-2. Journal of Applied Microbiology, 136(1), lxae301.
Mahavy, C. E., Duez, P., ElJaziri, M., & Rasamiravaka, T. (2020). African plant-based natural products with antivirulence activities to the rescue of antibiotics. Antibiotics, 9(11), 830. https://doi.org/https://doi.org/10.3390/antibiotics9110830
Mamur, S., Ünal, F., Y?lmaz, S., Erikel, E., & Yüzba??o?lu, D. (2020). Evaluation of the cytotoxic and genotoxic effects of mycotoxin fusaric acid. Drug and Chemical Toxicology, 43(2), 149-157.
Mao, Z., Zhang, W., Wu, C., Feng, H., Peng, Y., Shahid, H., Cui, Z., Ding, P., & Shan, T. (2021). Diversity and antibacterial activity of fungal endophytes from Eucalyptus exserta. BMC Microbiology, 21(1), 155.
Maroyi, A. (2023). Faurea saligna Harv. (Proteaceae): Medicinal uses and biological properties. Medicinal Plants - International Journal of Phytomedicines and Related Industries, 15, 645-653. https://doi.org/10.5958/0975-6892.2023.00065.5
Masevhe, N. A., McGaw, L. J., & Eloff, J. N. (2015). The traditional use of plants to manage candidiasis and related infections in Venda, South Africa. Journal of Ethnopharmacology, 168, 364-372. https://doi.org/http://dx.doi.org/10.1016/j.jep.2015.03.046
Mohamed, G. A., Ibrahim, S. R., & Asfour, H. Z. (2020). Antimicrobial metabolites from the endophytic fungus Aspergillus versicolor. Phytochemistry Letters, 35, 152-155.
Newman, D. J., & Cragg, G. M. (2020). Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019. Journal of Natural Products, 83(3), 770-803.
Nucci, M., & Anaissie, E. (2007). Fusarium infections in immunocompromised patients. Clinical Microbiology Reviews, 20(4), 695-704.
Nyagumbo, E., Pote, W., Shopo, B., Nyirenda, T., Chagonda, I., Mapaya, R. J., aunganidze F., Mavengere W. N., Mawere C., Mutasa I & Kademeteme E. (2022). Medicinal plants used for the management of respiratory diseases in Zimbabwe: Review and perspectives potential management of COVID-19. Physics and Chemistry of the Earth, Parts A/B/C, 128, 103232. https://doi.org/https://doi.org/10.1016/j.pce.2022.103232
Oosthuizen, C. B., Gasa, N., Hamilton, C. J., & Lall, N. (2019). Inhibition of mycothione disulphide reductase and mycobacterial biofilm by selected South African plants. South African Journal of Botany, 120, 291-297. https://doi.org/https://doi.org/10.1016/j.sajb.2018.09.015
Pal, S., Chatare, V., & Pal, M. (2011). Isocoumarin and its derivatives: An overview on their synthesis and applications. Current Organic Chemistry, 15(5), 782-800.
Pan, J.-H., Chen, Y., Huang, Y.-H., Tao, Y.-W., Wang, J., Li, Y., Lin, Peng Y., Dong T., Lai X. M. & Lin, Y.-C. (2011). Antimycobacterial activity of fusaric acid from a mangrove endophyte and its metal complexes. Archives of Pharmacal Research, 34(7), 1177-1181.
Paterson, J. R., Hardman, B. L., Jordan, L. A., Wadsworth, J. M., Black, D. J., Ross, J., J., Clare L. A., Wright E., Wallace E. R., Pal, R. & Moran M. T. (2025). Antibacterial chelating agents with applications in industry and medicine: cellular metal restriction, membrane disruption, and synergism with antibiotics in Escherichia coli, Pseudomonas aeruginosa, Serratia marcescens, Bacillus subtilis, and Staphylococcus aureus. Journal of Applied Microbiology, 136(11), lxaf258.
Rodrigo, S., García-Latorre, C., & Santamaria, O. (2021). Metabolites produced by fungi against fungal phytopathogens: Review, implementation and perspectives. Plants, 11(1), 81.
Sachs, J., Döhl, K., Weber, A., Bonus, M., Ehlers, F., Fleischer, E., Klinger A., Gohlke H., Pietruszka J., Schmitt, L. & Teusch N. (2019). Novel 3, 4-dihydroisocoumarins inhibit human P-gp and BCRP in multidrug resistant tumors and demonstrate substrate inhibition of yeast Pdr5. Frontiers in Pharmacology, 10, 400.
Saeed, A. (2016). Isocoumarins, miraculous natural products blessed with diverse pharmacological activities. European Journal of Medicinal Chemistry, 116, 290-317.
Schulz, B., Boyle, C., Draeger, S., Römmert, A.-K., & Krohn, K. (2002). Endophytic fungi: a source of novel biologically active secondary metabolites. Mycological Research, 106(9), 996-1004.
Seçme, M., Urganc?, A. B. E., Üzen, R., Aslan, A., & T?ra?, F. (2023). Determination of the effects of fusaric acid, a mycotoxin, on cytotoxicity, gamma-H2AX, 8-hydroxy-2 deoxyguanosine and DNA repair gene expressions in pancreatic cancer cells. Toxicon, 231, 107179.
Shi, S., Li, Y., Ming, Y., Li, C., Li, Z., Chen, J., & Luo, M. (2018). Biological activity and chemical composition of the endophytic fungus Fusarium sp. TP-G1 obtained from the root of Dendrobium officinale Kimura et Migo. Records of Natural Products, 12, 549-556.
Singh, A., Kumar, J., Sharma, V. K., Singh, D. K., Kumari, P., Nishad, J. H., Gautam V. S. & Kharwar, R. N. (2021). Phytochemical analysis and antimicrobial activity of an endophytic Fusarium proliferatum (ACQR8), isolated from a folk medicinal plant Cissus quadrangularis L. South African Journal of Botany, 140, 87-94.
Sondergaard, T. E., Fredborg, M., Oppenhagen Christensen, A.-M., Damsgaard, S. K., Kramer, N. F., Giese, H., & Sørensen, J. L. (2016). Fast screening of antibacterial compounds from Fusaria. Toxins, 8(12), 355.
Souza, R. B., Frota, A. F., Silva, J., Alves, C., Neugebauer, A. Z., Pinteus, S., Rodrigues J. A. G., Cordeiro E. M. S., Almeida R. R., & Pedrosa, R. (2018). In vitro activities of kappa-carrageenan isolated from red marine alga Hypnea musciformis: Antimicrobial, anticancer and neuroprotective potential. International Journal of Biological Macromolecules, 112, 1248-1256. https://doi.org/https://doi.org/10.1016/j.ijbiomac.2018.02.029
Stafford, G. I., Pedersen, M. E., van Staden, J., & Jäger, A. K. (2008). Review on plants with CNS-effects used in traditional South African medicine against mental diseases. Journal of Ethnopharmacology, 119(3), 513-537. https://doi.org/https://doi.org/10.1016/j.jep.2008.08.010
Št?pánek, O., ?moková, A., Procházková, E., Grobárová, V., ?erný, J., Slapni?ková, M., Zíková A., Kola?ík M., & Baszczy?ski, O. (2022). Piperazine?Modified Ketoconazole Derivatives Show Increased Activity against Fungal and Trypanosomatid Pathogens. ChemMedChem, 17(21), e202200385.
Summerell, B. A. (2019). Resolving Fusarium: Current status of the genus. Annual Review of Phytopathology, 57(1), 323-339.
Supratman, U., Hirai, N., Sato, S., Watanabe, K., Malik, A., Annas, S., Harneti D., Maharani R., Koseki T., & Shiono, Y. (2021). New naphthoquinone derivatives from Fusarium napiforme of a mangrove plant. Natural Product Research, 35(9), 1406-1412.
Tabopda, T. K., Fotso, G. W., Ngoupayo, J., Mitaine-Offer, A.-C., Ngadjui, B. T., & Lacaille-Dubois, M.-A. (2009). Antimicrobial dihydroisocoumarins from Crassocephalum biafrae. Planta Medica, 75(11), 1258-1261.
Thanh, T. T., Quoc, T. N., & Xuan, H. L. (2020). Fusaric acid and derivatives as novel antimicrobial agents. Medicinal Chemistry Research, 29(9), 1689-1696.
Tshikalange, T. E., Mophuting, B. C., Mahore, J., Winterboer, S., & Lall, N. (2016). An ethnobotanical study of medicinal plants used in villages under Jongilanga tribal council, Mpumalanga, South Africa. African Journal of Traditional, Complementary and Alternative Medicines, 13(6), 83-89. https://doi.org/https://doi.org/10.21010/ajtcam.v13i6.13
Tung, T. T., Jakobsen, T. H., Dao, T. T., Fuglsang, A. T., Givskov, M., Christensen, S. B., & Nielsen, J. (2017). Fusaric acid and analogues as Gram-negative bacterial quorum sensing inhibitors. European Journal of Medicinal Chemistry, 126, 1011-1020.
Xiao, Z. e., Chen, S., Cai, R., Lin, S. e., Hong, K., & She, Z. (2016). New furoisocoumarins and isocoumarins from the mangrove endophytic fungus Aspergillus sp. 085242. Beilstein Journal of Organic Chemistry, 12(1), 2077-2085.
Xu, G.-B., Yang, F.-Y., Wu, X.-Y., Li, R., Zhou, M., Wang, B., Yang X. -S., Zhang T. -T., & Liao, S.-G. (2021). Two new dihydroisocoumarins with antimicrobial activities from the fungus Penicillium sp. XR046 collected from Xinren coal area. Natural Product Research, 35(9), 1445-1451.
Zhang, Q. Y., Yang, F. Y., Liao, S. G., Wang, B., Li, R., Dong, Y. X., Zhou M., Yang Y. Y. & Xu, G. B. (2021). Synthesis, antibacterial activity, and structure–activity relationship of fusaric acid analogs. Bulletin of the Korean Chemical Society, 42(4), 577-582.
Zhou, G., Qiao, L., Zhang, X., Sun, C., Che, Q., Zhang, G., Zhu T., Gu Q. & Li, D. (2019). Fusaricates HK and fusolanones AB from a mangrove endophytic fungus Fusarium solani HDN15-410. Phytochemistry, 158, 13-19.
DOI: https://doi.org/10.14421/biomedich.2026.152.1933-1942
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