A detailed chemical investigation of the Australian pasture soil-derived Actinomadura sp. S4S-00069B10, utilizing optimized cultivation on four different solid-phase media (M1, IMA, D400, and YEME), yielded the new isoindolinone goondicones I-K (1-3) and anthra-γ-pyrone cratermycins A-D (4-7). Structures were assigned to 1-7 on the basis of detailed spectroscopic, ECD, and X-ray analyses as well as chemical transformations and biosynthetic considerations. The goondicones 1-3 are especially noteworthy in that they feature an unprecedented carbo-heterocyclic framework, with 1 and 2 undergoing a facile keto-enol-mediated equilibration to a 1:3 mixture (of C-13 epimers) that exhibits promising anthelmintic properties against the dog heartworm Dirofilaria immitis microfilariae (EC50 1.1 μM) and L4 larvae (EC50 1.3 μM). Notably, this activity is accompanied by measurable mammalian cytotoxicity, indicating a narrow therapeutic window. Together, these findings highlight the chemical novelty of Actinomadura-derived metabolites, and their value as structurally unique anthelmintics leads to further optimization.
Han et al. (Thu,) studied this question.