Biosynthetically Distinct Cytotoxic Polyketides from Setophoma terrestris

Sixteen polyketides belonging to diverse structural classes, including monomeric/dimeric tetrahydroxanthones and resorcylic acid lactones, were isolated from an organic extract of a fungal culture Setophoma terrestris (MSX45109) by bioactivity‐directed fractionation as part of a search for anticancer leads from filamentous fungi. Of these, six were new: penicillixanthone B (5), blennolide H (6), 11‐deoxyblennolide D (7), blennolide I (9), blennolide J (10), and pyrenomycin (16). The known compounds were: secalonic acid A (1), secalonic acid E (2), secalonic acid G (3), penicillixanthone A (4), paecilin B (8), aigialomycin A (11), hypothemycin (12), dihydrohypothemycin (13), pyrenochaetic acid C (14), and nidulalin B (15). The structures were elucidated by a set of spectroscopic and spectrometric techniques: the absolute configurations of compounds 1–10 were determined by ECD spectroscopy combined with time‐dependent density functional theory (TDDFT) calculations, whereas a modified Mosher's ester method was used for compound 16. The cytotoxic activities of compounds 1–15 against the MDA‐MB‐435 (melanoma) and SW‐620 (colon) cancer cell lines were evaluated. Compounds 1, 4, and 12 were the most potent, with IC50 values ranging from 0.16 to 2.14 μM. When tested against a panel of bacteria and fungi, compounds 3 and 5 showed promising activity against the Gram‐positive bacterium Micrococcus luteus, with MIC values of 5 and 15 μg mL–1, respectively.