Phialocephala scopiformis (Ascomycota, Helotiales, Mollisiaceae) are fungi known as both saprophytes and endophytes, forming small apothecia (1 - 3 mm in diameter) on decaying wood. In this study, three novel isocoumarin derivatives (+)-phaeosphaerin A (1), (+)-phaeosphaerin B (2), and (S)-6-demethylkigelin (3) were isolated from Phialocephala scopiformis FC-1873 collected in Japan, along with two known isocoumarins, lignicol (4) and 6,8-dihydroxy-3,5-dimethyl-1H-2-benzopyran-1-one (5). The cytotoxicity of 1 and 4 were evaluated against HL-60, PANK-1, HepG2, HT-29, and T98G cell lines, as well as their effects on cell proliferation in the skin keratinocyte cell line HaCaT. These findings highlight the potential of mollisioid fungi as a source of novel bioactive compounds.
References
[1]
Tanney, J.B., Douglas, B. and Seifert, K.A. (2016) Sexual and Asexual States of Some Endophytic Phialocephala Species of Picea. Mycologia, 108, 255-280. https://doi.org/10.3852/15-136
[2]
Miller, J.D., Mackenzie, S., Foto, M., Adams, G.W. and Findlay, J.A. (2002) Needles of White Spruce Inoculated with Rugulosin-Producing Endophytes Contain Rugulosin Reducing Spruce Budworm Growth Rate. MycologicalResearch, 106, 471-479. https://doi.org/10.1017/s0953756202005671
[3]
Tanimoto, T., Hamano, K., Onodera, K., Hosoya, T., Kakusaka, M., Hirayama, T., et al. (1997) Biological Activities of Novel Zaragozic Acids, the Potent Inhibitors of Squalene Synthase, Produced by the Fungus, Mollisia Sp. SANK 10294. TheJournalofAntibiotics, 50, 390-394. https://doi.org/10.7164/antibiotics.50.390
[4]
Thines, E., Arendholz, W., Anke, H. and Sterner, O. (1997) Benesudon, a New Antibiotic Fungal Metabolite from Cultures of Mollisia benesuada (tul.) Phill. TheJournalofAntibiotics, 50, 13-17. https://doi.org/10.7164/antibiotics.50.13
[5]
Weber, D., Sterner, O. and Anke, T. (2007) Mollisianitrile, a New Antibiotic from Mollisia sp. A59-96. ZeitschriftfürNaturforschungC, 62, 567-570. https://doi.org/10.1515/znc-2007-7-817
[6]
Nakanishi, S., Ando, K., Kawamoto, I., Yasuzawa, T., Sano, H. and Kase, H. (1989) KS-504 Compounds, Novel Inhibitors of Ca2+ and Calmodulin-Dependent Cyclic Nucleotide Phosphodiesterase from Mollisia ventosa. TheJournalofAntibiotics, 42, 1775-1783. https://doi.org/10.7164/antibiotics.42.1775
[7]
Rether, J., Erkel, G., Sterner, O. and Anke, T. (2005) Inhibition of TNF-α Promoter Activity and Synthesis by A11-99-1, a New Cyclopentenone from the Ascomycete Mollisia melaleuca. ZeitschriftfürNaturforschungC, 60, 478-484. https://doi.org/10.1515/znc-2005-5-617
[8]
Cai, J., Wang, X., Gan, X., Zhou, Q., Luo, X., Yang, B., et al. (2022) New Chlorinated Metabolites and Antiproliferative Polyketone from the Mangrove Sediments-Derived Fungus Mollisia sp. SCSIO41409. MarineDrugs, 21, Article 32. https://doi.org/10.3390/md21010032
[9]
Ayer, W.A., Lu, P., Orszanska, H. and Sigler, L. (1993) Deoxyscytalidin and Lignicol: New Metabolites from Scytalidium Species. JournalofNaturalProducts, 56, 1835-1838. https://doi.org/10.1021/np50100a029
[10]
Nakajima, T., Kuroda, A., Tsuji, E. and Yoshida, M. (2002) Isocoumarins and Bronchodilators Containing Them. JP Patent, 2002-1610.
[11]
Prajapati, J., Goswami, D. and Rawal, R.M. (2021) Endophytic Fungi: A Treasure Trove of Novel Anticancer Compounds. CurrentResearchinPharmacologyandDrugDiscovery, 2, Article ID: 100050. https://doi.org/10.1016/j.crphar.2021.100050
Hothorn, T., Bretz, F. and Westfall, P. (2008) Simultaneous Inference in General Parametric Models. BiometricalJournal, 50, 346-363. https://doi.org/10.1002/bimj.200810425
[14]
Wang, P., Wang, H., Yang, J., Yang, L., Cai, C., Yuan, J., et al. (2023) New Isocoumarins from the Marine Fungus Phaeosphaeriopsis sp. WP-26. MarineDrugs, 21, Article 150. https://doi.org/10.3390/md21030150
[15]
Shimada, A., Inokuchi, T., Kusano, M., Takeuchi, S., Inoue, R., Tanita, M., et al. (2004) 4-Hydroxykigelin and 6-Demethylkigelin, Root Growth Promoters, Produced by Aspergillus Terreus. ZeitschriftfürNaturforschungC, 59, 218-222. https://doi.org/10.1515/znc-2004-3-417
[16]
Ghandi, M., Huang, F.W., Jané-Valbuena, J., Kryukov, G.V., Lo, C.C., McDonald, E.R., et al. (2019) Next-Generation Characterization of the Cancer Cell Line Encyclopedia. Nature, 569, 503-508. https://doi.org/10.1038/s41586-019-1186-3
[17]
Ruttanapattanakul, J., Wikan, N., Okonogi, S., Na Takuathung, M., Buacheen, P., Pitchakarn, P., et al. (2021) Boesenbergia rotunda Extract Accelerates Human Keratinocyte Proliferation through Activating ERK1/2 and PI3K/Akt Kinases. Biomedicine&Pharmacotherapy, 133, Article ID: 111002. https://doi.org/10.1016/j.biopha.2020.111002
[18]
Kim, J., Shin, Y. and Kim, K. (2018) Promotion of Keratinocyte Proliferation by Tracheloside through ERK1/2 Stimulation. Evidence-BasedComplementaryandAlternativeMedicine, 2018, Article ID: 4580627. https://doi.org/10.1155/2018/4580627
[19]
Zhang, W. and Liu, H.T. (2002) MAPK Signal Pathways in the Regulation of Cell Proliferation in Mammalian Cells. CellResearch, 12, 9-18. https://doi.org/10.1038/sj.cr.7290105
[20]
Liu, M., Zhou, D., Liu, Q., Xie, F., Xiang, D., Tang, G., et al. (2019) Osteogenesis Activity of Isocoumarin a through the Activation of the PI3K-Akt/Erk Cascade-Activated BMP/RUNX2 Signaling Pathway. EuropeanJournalofPharmacology, 858, Article ID: 172480. https://doi.org/10.1016/j.ejphar.2019.172480
