title: Cytotoxic constituents of Aspergillus terreus from the rhizosphere of Opuntia versicolor of the Sonoran Desert.
abstract: A novel cyclopentenedione, asterredione (1), two new terrecyclic acid A derivatives, (+)-5(6)-dihydro-6-methoxyterrecyclic acid A (2) and (+)-5(6)-dihydro-6-hydroxyterrecyclic acid A (3), and five known compounds, (+)-terrecyclic acid A (4), (-)-quadrone (5), betulinan A (6), asterriquinone D (7), and asterriquinone C-1 (8), were isolated from Aspergillus terreus occurring in the rhizosphere of Opuntia versicolor, using bioassay-guided fractionation. Acid-catalyzed reaction of 2 under mild conditions afforded 4, whereas under harsh conditions 2 yielded 5 and (-)-isoquadrone (9). Catalytic hydrogenation and methylation of 4 afforded 5(6)-dihydro-terrecyclic acid A (10) and (+)-terrecyclic acid A methyl ester (11), respectively. The structures of 1-11 were elucidated by spectroscopic methods. All compounds were evaluated for cytotoxicity in a panel of three sentinel cancer cell lines, NCI-H460 (non-small cell lung cancer), MCF-7 (breast cancer), and SF-268 (CNS glioma), and were found to be moderately active. Cell cycle analysis of 2, 4, and 5 using the NCI-H460 cell line indicated that 4 is capable of disrupting the cell cycle through an apparent arrest to progression at the G(1) and G(2)/M phases in this p53 competent cell line. A pathway for the biosynthetic origin of asterredione (1) from asterriquinone D (7) is proposed.
authors.affiliation: SW Center for Natural Products Research and Commercialization, Office of Arid Lands Studies, College of Agriculture and Life Sciences, University of Arizona, 250 E. Valencia Road, Tucson, Arizona 85706-6800, USA.
authors.forename: E M Kithsiri
authors.initials: EM
authors.lastname: Wijeratne
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Turbyville
authors.forename: Zhongge
authors.initials: Z
authors.lastname: Zhang
authors.forename: Donna
authors.initials: D
authors.lastname: Bigelow
authors.forename: Leland S
authors.initials: LS
authors.lastname: Pierson
authors.forename: Hans D
authors.initials: HD
authors.lastname: VanEtten
authors.forename: Luke
authors.initials: L
authors.lastname: Whitesell
authors.forename: Louise M
authors.initials: LM
authors.lastname: Canfield
authors.forename: A A Leslie
authors.initials: AA
authors.lastname: Gunatilaka
mesh_terms: D000970:Antineoplastic Agents / Q000302:isolation & purification* / Q000494:pharmacology; D001130:Arizona; D001230:Aspergillus / Q000737:chemistry*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D003517:Cyclopentanes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D003889:Desert Climate; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D015394:Molecular Structure; D009423:Nervous System Neoplasms; D019906:Nuclear Magnetic Resonance, Biomolecular; D029747:Opuntia; D013237:Stereoisomerism
chemical_list: D000970:Antineoplastic Agents; D003517:Cyclopentanes; D007211:Indoles; C482764:asterredione