Cytotoxic constituents of Aspergillus terreus from the rhizosphere of Opuntia versicolor of the Sonoran Desert. Academic Article uri icon

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.

published proceedings

  • J Nat Prod

author list (cited authors)

  • Wijeratne, E., Turbyville, T. J., Zhang, Z., Bigelow, D., Pierson, L. S., VanEtten, H. D., ... Gunatilaka, A.

citation count

  • 56

complete list of authors

  • Wijeratne, EM Kithsiri||Turbyville, Thomas J||Zhang, Zhongge||Bigelow, Donna||Pierson, Leland S||VanEtten, Hans D||Whitesell, Luke||Canfield, Louise M||Gunatilaka, AA Leslie

publication date

  • December 2003