Biosynthetically Distinct Cytotoxic Polyketides from Setophoma terrestris

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Tamam M. El-Elimat (Creator)
Mario Figueroa Saldivar (Creator)
Tyler Graf, Research Scientist (Creator)
Nicholas Oberlies, Patricia A. Sullivan Distinguished Professor of Chemistry (Creator)
Cedric J Pearce, Adjunct Professor (Creator)
Huzefa A. Raja, Postdoctoral Fellow (Creator)
Mansukhlal Chhaganlal Wani (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/

Abstract: 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 12were 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.

Additional Information

Publication
European Journal of Organic Chemistry, 2015: 109-121. doi:10.1002/ejoc.201402984
Language: English
Date: 2015
Keywords
Natural products, Polyketides, Medicinal chemistry, Cytotoxicity, Antitumor agents, Configuration determination, Structure–activity relationships

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