title: Biosynthetically Distinct Cytotoxic Polyketides fromSetophoma terrestris.
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 cultureSetophoma terrestris(MSX45109) using 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-deoxy blennolide 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 using a set of spectroscopic and spectrometric techniques; the absolute configurations of compounds1-10were determined using ECD spectroscopy combined with time-dependent density functional theory (TDDFT) calculations, while a modified Mosher's ester method was used for compound16. The cytotoxic activities of compounds (1-15) were evaluated using the MDA-MB-435 (melanoma) and SW-620 (colon) cancer cell lines. Compounds1,4, and12were the most potent with IC50values ranging from 0.16 to 2.14 μM. When tested against a panel of bacteria and fungi, compounds3and5showed promising activity against the Gram-positive bacteriumMicrococcus luteuswith MIC values of 5 and 15 μg/mL, respectively.
authors.affiliation: Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC 27402, United States, Homepage: http://www.uncg.edu/che/Group_Research_Page/NicholasOberlies.
authors.forename: Tamam
authors.initials: T
authors.lastname: El-Elimat
authors.affiliation: Facultad de Química, Universidad Nacional Autónoma de México Mexico DF 04510, Mexico.
authors.forename: Mario
authors.initials: M
authors.lastname: Figueroa
authors.affiliation: Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC 27402, United States, Homepage: http://www.uncg.edu/che/Group_Research_Page/NicholasOberlies.
authors.forename: Huzefa A
authors.initials: HA
authors.lastname: Raja
authors.affiliation: Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC 27402, United States, Homepage: http://www.uncg.edu/che/Group_Research_Page/NicholasOberlies.
authors.forename: Tyler N
authors.initials: TN
authors.lastname: Graf
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy University of Illinois at Chicago, Chicago, IL 60612, United States.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Swanson
authors.affiliation: Department of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, United States.
authors.forename: Joseph O
authors.initials: JO
authors.lastname: Falkinham
authors.affiliation: Natural Products Laboratory, Research Triangle Institute, Research Triangle Park NC 27709 United States.
authors.forename: Mansukh C
authors.initials: MC
authors.lastname: Wani
authors.affiliation: Mycosynthetix Inc., Hillsborough, NC 27278, United States.
authors.forename: Cedric J
authors.initials: CJ
authors.lastname: Pearce
authors.affiliation: Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC 27402, United States, Homepage: http://www.uncg.edu/che/Group_Research_Page/NicholasOberlies.
authors.forename: Nicholas H
authors.initials: NH
authors.lastname: Oberlies
keywords: Cytotoxicity; ergochromes; fungus; resorcylic acid lactones; secalonic acids