Goondapyrones A-J: Polyketide α and γ Pyrone Anthelmintics from an Australian Soil-Derived sp.

An investigation of ×19 soil samples collected under the auspices of the Australian citizen science initiative, Soils for Science, returned ×559 chemically dereplicated microbial isolates, of which ×54 exhibited noteworthy anthelmintic activity against either the heartworm microfilaria and/or the gastrointestinal parasite L1-L3 larvae. Chemical (GNPS and UPLC-DAD) and cultivation (MATRIX) profiling prompted a detailed chemical investigation of sp. S4S-00196A10, which yielded new anthelmintic polyketide goondapyrones A-J (-), together with the known actinopyrones A () and C (). Structures for - were assigned on the basis of detailed spectroscopic and chemical analysis, with preliminary structure activity relationship analysis revealing selected γ-pyrones >50-fold and >13-fold more potent than isomeric α-pyrones against mf motility (e.g., EC 0.05 μM for ; EC 2.7 μM for ) and L1-L3 larvae development (e.g., EC 0.58 μM for ; EC 8.2 μM for ), respectively.