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Marine actinomycetes are prolific chemical sources of complex and novel natural products, providing an excellent chance for new drug discovery. The chemical investigation of the marine-derived Streptomyces sp. ITBB-ZKa6, from Zhaoshu island, Hainan, led to the discovery of two unique antimycin-type depsipeptides, zhaoshumycins A ( 1 ) and B ( 2 ), along with the isolation of the four known neoantimycins A ( 3 ), F ( 4 ), D ( 5 ), and E ( 6 ). The structures of the new compounds 1 and 2 were elucidated on the basis of the analysis of diverse spectroscopic data and biogenetic consideration. Zhaoshumycins A ( 1 ) and B ( 2 ) represent a new class of depsipeptides, featuring two neoantimycin monomers (only neoantimycin D or neoantimycins D and E) linked to a 1,4-disubstituted benzene ring via an imino group. Initial toxicity tests of 1 - 6 in MCF7 human breast cancer cells revealed that compounds 5 and 6 possess weak cytotoxic activity. Further structure-activity relationship analysis suggested the importance of the NH 2 group at C-34 in 5 and 6 for cytotoxicity in MCF7 cells.

Zhaoshumycins A and B, Two Unprecedented Antimycin-Type Depsipeptides Produced by the Marine-Derived Streptomyces sp. ITBB-ZKa6