Antitumor Agents. 282. 2'-(R)-O-acetylglaucarubinone, a quassinoid from Odyendyea gabonensis as a potential anti-breast and anti-ovarian cancer agent

  • J Nat Prod. 2010 Sep 24;73(9):1553-8. doi: 10.1021/np100406d.
Yoshihide Usami  1 ,  Kyoko Nakagawa-Goto ,  Jing-Yu Lang ,  Yoon Kim ,  Chin-Yu Lai ,  Masuo Goto ,  Nobuko Sakurai ,  Masahiko Taniguchi ,  Toshiyuki Akiyama ,  Susan L Morris-Natschke ,  Kenneth F Bastow ,  Gordon Cragg ,  David J Newman ,  Mihoyo Fujitake ,  Koichi Takeya ,  Mien-Chie Hung ,  Eva Y-H P Lee ,  Kuo-Hsiung Lee
Affiliations
  • 1. Natural Products Research Laboratories, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599-7568, USA.
PMID: 20738103 DOI: 10.1021/np100406d
Abstract

A new quassinoid, designated 2'-(R)-O-acetylglaucarubinone (1), and seven known quassinoids (2-8) were isolated, using bioactivity-guided separation, from the bark of Odyendyea gabonensis (Pierre) Engler [syn. Quassia gabonensis Pierre]. The structure of 1 was determined by spectroscopic analysis and by semisynthesis from glaucarubolone. Complete (1)H and (13)C NMR assignments of compounds 1-8 were also established from detailed analysis of two-dimensional NMR spectra, and the reported configurations in odyendene (7) and odyendane (8) were corrected. Compound 1 showed potent cytotoxicity against multiple Cancer cell lines. Further investigation using various types of breast and Ovarian Cancer cell lines suggested that 1 does not target the Estrogen Receptor or Progesterone Receptor. When tested against mammary epithelial proliferation in vivo using a Brca1/p53-deficient mice model, 1 also caused significant reduction in mammary duct branching.