Sheptide A: an antimalarial cyclic pentapeptide from a fungal strain in the Herpotrichiellaceae

As part of ongoing efforts to isolate biologically active fungal metabolites, a cyclic pentapeptide, sheptide A (1), was discovered from strain MSX53339 (Herpotrichiellaceae). The structure and sequence of 1 were determined primarily by analysis of 2D NMR and HRMS/MS data, while the absolute configu...

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Detalles Bibliográficos
Autores principales: Shepherd, Robert A., Earp, Cody E., Cank, Kristof B., Raja, Huzefa A., Burdette, Joanna, Maher, Steven P., Marin, Adriana A., Ruberto, Anthony A., Mai, Sarah Lee, Darveaux, Blaise A., Kyle, Dennis E., Pearce, Cedric J., Oberlies, Nicholas H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Japan 2023
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10602849/
https://www.ncbi.nlm.nih.gov/pubmed/37731043
http://dx.doi.org/10.1038/s41429-023-00655-6
Descripción
Sumario:As part of ongoing efforts to isolate biologically active fungal metabolites, a cyclic pentapeptide, sheptide A (1), was discovered from strain MSX53339 (Herpotrichiellaceae). The structure and sequence of 1 were determined primarily by analysis of 2D NMR and HRMS/MS data, while the absolute configuration was assigned using a modified version of Marfey’s method. In an in vitro assay for antimalarial potency, 1 displayed a pEC(50) value of 5.75 ± 0.49 against malaria-causing Plasmodium falciparum. Compound 1 was also tested in a counter screen for general cytotoxicity against human hepatocellular carcinoma (HepG2), yielding a pCC(50) value of 5.01 ± 0.45 and indicating a selectivity factor of ~6. This makes 1 the third known cyclic pentapeptide biosynthesized by fungi with antimalarial activity.

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