Cytotoxic constituents of Aspergillus terreus from the rhizosphere of Opuntia versicolor of the Sonoran Desert.
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.
Wijeratne
E M Kithsiri
EM
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.
Turbyville
Thomas J
TJ
Zhang
Zhongge
Z
Bigelow
Donna
D
Pierson
Leland S
LS
VanEtten
Hans D
HD
Whitesell
Luke
L
Canfield
Louise M
LM
Gunatilaka
A A Leslie
AA
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
D000970:Antineoplastic Agents; D003517:Cyclopentanes; D007211:Indoles; C482764:asterredione