Biosynthetically Distinct Cytotoxic Polyketides from .

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 (MSX45109) using bioactivity-directed fractionation as part of a search for anticancer leads from filamentous fungi. Of these, six were new: penicillixanthone B (), blennolide H (), 11-deoxy blennolide D (), blennolide I (), blennolide J (), and pyrenomycin (). The known compounds were: secalonic acid A (), secalonic acid E (), secalonic acid G (), penicillixanthone A (), paecilin B (), aigialomycin A (), hypothemycin (), dihydrohypothemycin (), pyrenochaetic acid C (), and nidulalin B (). The structures were elucidated using a set of spectroscopic and spectrometric techniques; the absolute configurations of compounds - were determined using ECD spectroscopy combined with time-dependent density functional theory (TDDFT) calculations, while a modified Mosher's ester method was used for compound . The cytotoxic activities of compounds (-) were evaluated using the MDA-MB-435 (melanoma) and SW-620 (colon) cancer cell lines. Compounds , , and were the most potent with IC values ranging from 0.16 to 2.14 μM. When tested against a panel of bacteria and fungi, compounds and showed promising activity against the Gram-positive bacterium with MIC values of 5 and 15 μg/mL, respectively.