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

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.