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 IC 50 values ranging from 0.16 to 2.14 μ M . 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.