Cytotoxic constituents of Aspergillus terreus from the rhizosphere of Opuntia versicolor of the Sonoran Desert

J Nat Prod. 2003 Dec;66(12):1567-73. doi: 10.1021/np030266u.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antineoplastic Agents / isolation & purification*
  • Antineoplastic Agents / pharmacology
  • Arizona
  • Aspergillus / chemistry*
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cyclopentanes / chemistry
  • Cyclopentanes / isolation & purification*
  • Cyclopentanes / pharmacology
  • Desert Climate
  • Drug Screening Assays, Antitumor
  • Humans
  • Indoles / chemistry
  • Indoles / isolation & purification*
  • Indoles / pharmacology
  • Molecular Structure
  • Nervous System Neoplasms
  • Nuclear Magnetic Resonance, Biomolecular
  • Opuntia
  • Stereoisomerism


  • Antineoplastic Agents
  • Cyclopentanes
  • Indoles
  • asterredione