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 <i>Dirofilaria immitis</i> microfilaria and/or the gastrointestinal parasite <i>Haemonchus contortus</i> L1-L3 larvae. Chemical (GNPS and UPLC-DAD) and cultivation (MATRIX) profiling prompted a detailed chemical investigation of <i>Streptomyces</i> sp. S4S-00196A10, which yielded new anthelmintic polyketide goondapyrones A-J (<b>1</b>-<b>10</b>), together with the known actinopyrones A (<b>11</b>) and C (<b>12</b>). Structures for <b>1</b>-<b>12</b> 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 <i>D. immitis</i> mf motility (e.g., EC₅₀ 0.05 μM for <b>1</b>; EC₅₀ 2.7 μM for <b>5</b>) and <i>H. contortus</i> L1-L3 larvae development (e.g., EC₅₀ 0.58 μM for <b>1</b>; EC₅₀ 8.2 μM for <b>5</b>), respectively.