Cytotoxic Constituents of Aspergillus terreus from the Rhizosphere of Opuntia versicolor of the Sonoran Desert

E. M.Kithsiri Wijeratne, Thomas J. Turbyville, Zhongge Zhang, Donna Bigelow, Leland S. Pierson, Hans D. VanEtten, Luke Whitesell, Louise M. Canfield, A. A.Leslie Gunatilaka

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57 Scopus citations

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 G1 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.

Original languageEnglish (US)
Pages (from-to)1567-1573
Number of pages7
JournalJournal Of Natural Products
Volume66
Issue number12
DOIs
StatePublished - Dec 1 2003

ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

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    Wijeratne, E. M. K., Turbyville, T. J., Zhang, Z., Bigelow, D., Pierson, L. S., VanEtten, H. D., Whitesell, L., Canfield, L. M., & Gunatilaka, A. A. L. (2003). Cytotoxic Constituents of Aspergillus terreus from the Rhizosphere of Opuntia versicolor of the Sonoran Desert. Journal Of Natural Products, 66(12), 1567-1573. https://doi.org/10.1021/np030266u