title: Cytotoxic and other metabolites of Aspergillus inhabiting the rhizosphere of Sonoran desert plants.
abstract: In a study to discover potential anticancer agents from rhizosphere fungi of Sonoran desert plants cytotoxic EtOAc extracts of four Aspergillus strains have been investigated. Two new metabolites, terrequinone A (1) and terrefuranone (2), along with Na-acetyl aszonalemin (LL-S490beta) (3) were isolated from As. terreus occurring in the rhizosphere of Ambrosia ambrosoides, whereas As. terreus inhabiting the rhizosphere of an unidentified Brickellia sp. afforded dehydrocurvularin (4), 11-methoxycurvularin (5), and 11-hydroxycurvularin (6). As. cervinus isolated from the rhizosphere of Anicasanthus thurberi contained two new compounds, 4R*,5S*-dihydroxy-3-methoxy-5-methylcyclohex-2-enone (7) and 6-methoxy-5(6)-dihydropenicillic acid (8), in addition to penicillic acid (9). Penicillic acid was also isolated from As. wentii occurring in the rhizosphere of Larrea tridentata. The structures of 1-9 were elucidated by spectroscopic methods and chemical derivatizations. Acetylation of 2 afforded 14-acetylterrefuranone (13) and 14-deoxy-13(14)-dehydroterrefuranone (14). Metabolites 1-9, the dienone 14, and 5(6)-dihydropenicillic acid (16) were evaluated for cytotoxicity in a panel of four human cancer cell lines and in normal human primary fibroblast cells. Compounds 4 and 5 displayed considerable cytotoxicity, whereas 1, 6, 9, and 14 were found to be moderately active, with 6 and 9 exhibiting selective cytotoxicity against cancer cell lines compared with the normal fibroblast cells.
authors.affiliation: Southwest 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: Jian
authors.initials: J
authors.lastname: He
authors.forename: E M Kithsiri
authors.initials: EM
authors.lastname: Wijeratne
authors.forename: Bharat P
authors.initials: BP
authors.lastname: Bashyal
authors.forename: Jixun
authors.initials: J
authors.lastname: Zhan
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Seliga
authors.forename: Manping X
authors.initials: MX
authors.lastname: Liu
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Pierson
authors.forename: Leland S
authors.initials: LS
authors.lastname: Pierson
authors.forename: Hans D
authors.initials: HD
authors.lastname: VanEtten
authors.forename: A A Leslie
authors.initials: AA
authors.lastname: Gunatilaka
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D001130:Arizona; D001230:Aspergillus / Q000737:chemistry*; D045744:Cell Line, Tumor; D003889:Desert Climate; D004354:Drug Screening Assays, Antitumor; D005663:Furans / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010398:Penicillic Acid / Q000737:chemistry / Q000302:isolation & purification; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D005663:Furans; D007211:Indoles; C496936:terrefuranone; C496935:terrequinone A; D010398:Penicillic Acid