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

Author:

Shepherd Robert A.,Earp Cody E.,Cank Kristof B.,Raja Huzefa A.ORCID,Burdette JoannaORCID,Maher Steven P.,Marin Adriana A.,Ruberto Anthony A.ORCID,Mai Sarah Lee,Darveaux Blaise A.,Kyle Dennis E.,Pearce Cedric J.ORCID,Oberlies Nicholas H.ORCID

Abstract

AbstractAs 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 pEC50 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 pCC50 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.

Funder

U.S. Department of Health & Human Services | NIH | National Cancer Institute

U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases

National Science Foundation

Publisher

Springer Science and Business Media LLC

Subject

Drug Discovery,Pharmacology

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