Wollamides: Antimycobacterial Cyclic Hexapeptides from an Australian Soil <i>Streptomyces</i>

Abstract

A soil <i>Streptomyces</i> 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 (<b>1</b> and <b>2</b>) and E and F (<b>3</b> and <b>4</b>), respectively, together with two new d-Orn homologues, wollamides A and B (<b>5</b> and <b>6</b>). 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