Wollamides: antimycobacterial cyclic hexapeptides from an Australian soil Streptomyces.

A soil Streptomyces nov. sp. (MST-115088) isolated from semiarid terrain near Wollogorang Station, Queensland, returned two known and two new examples of a rare class of cyclic hexapeptide, desotamides A and B (1 and 2) and E and F (3 and 4), respectively, together with two new d-Orn homologues, wollamides A and B (5 and 6). Structures were assigned by detailed spectroscopic and C3 Marfey's analysis. The desotamides/wollamides exhibit growth inhibitory activity against Gram-positive bacteria (IC50 0.6-7 μM) and are noncytotoxic to mammalian cells (IC50 >30 μM). The wollamides exhibit antimycobacterial activity (IC50 2.8 and 3.1 μM), including reduction in the intracellular mycobacterial survival in murine bone marrow-derived macrophages.