Goondapyrones A-J: Polyketide α and γ Pyrone Anthelmintics from an Australian Soil-Derived Streptomyces 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 Dirofilaria immitis microfilaria and/or the gastrointestinal parasite Haemonchus contortus L1-L3 larvae. Chemical (GNPS and UPLC-DAD) and cultivation (MATRIX) profiling prompted a detailed chemical investigation of Streptomyces sp. S4S-00196A10, which yielded new anthelmintic polyketide goondapyrones A-J (1-10), together with the known actinopyrones A (11) and C (12). Structures for 1-12 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 D. immitis mf motility (e.g., EC(50) 0.05 μM for 1; EC(50) 2.7 μM for 5) and H. contortus L1-L3 larvae development (e.g., EC(50) 0.58 μM for 1; EC(50) 8.2 μM for 5), respectively.