Goondomycins A-H: Carbocyclic ansa-Polyketides from an Australian Pasture Streptomyces with Selective Activity against Dirofilaria immitis

Abstract

A bioassay-guided chemical investigation of an Australian pasture-soil-derived Streptomyces sp. yielded the rare carbocyclic ansa-polyketide kendomycin (1) along with a series of new analogues, goondomycins A-H (2-9), featuring unprecedented carbo/heterocyclic scaffolds and chromophores, with structures assigned by detailed spectroscopic analysis, chemical and biochemical transformations, and biosynthetic considerations. Goondomycins B (2) and F (7) are noteworthy in being potent motility inhibitors of heartworm Dirofilaria immitis microfilaria (EC₅₀ 0.3 and 0.5 μM) and L4 larvae (EC₅₀ 1.4 and 1.8 μM), while exhibiting no significant antibacterial and antifungal activity or cytotoxicity to mammalian cells.