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 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 similar to 6. This makes 1 the third known cyclic pentapeptide biosynthesized by fungi with antimalarial activity.

Automated summary

A cyclic pentapeptide called sheptide A was discovered from a strain of Herpotrichiellaceae fungi. It showed antimalarial activity against Plasmodium falciparum in vitro, as well as selective cytotoxicity against human hepatocellular carcinoma cells.