Zygosporamide, a cytotoxic cyclic depsipeptide from the marine-derived fungus Zygosporium masonii

Zygosporamide (1), a new cyclic pentadepsipeptide, was isolated from the seawater-based fermentation broth of a marine-derived fungus identified as Zygosporium masonii. The structure of 1, which is composed of α-hydroxyleucic acid and both d- and l-amino acids, was determined by combined spectral and chemical methods. Despite a simple structure, zygosporamide illustrated significant cytotoxicity in the NCI’s 60 cell line panel (median GI₅₀ = 9.1 μM), with highly enhanced selectivity against the CNS cancer cell line SF-268 (GI₅₀ = 6.5 nM) and the renal cancer cell line RXF 393 (GI₅₀ ? 5.0 nM).