Design, synthesis and biological evaluation of novel triaryl (Z)-olefins as tamoxifen analogues

  • Bioorg Med Chem Lett. 2013 Sep 1;23(17):4960-3. doi: 10.1016/j.bmcl.2013.06.056.
Khaled R A Abdellatif  1 ,  Amany Belal ,  Hany A Omar
Affiliations
  • 1. Department of Pharmaceutical Organic Chemistry, Beni-Suef University, Beni-Suef 62514, Egypt. [email protected]
PMID: 23860592 DOI: 10.1016/j.bmcl.2013.06.056
Abstract

Tamoxifen (TAM) is used for the treatment and prevention of Estrogen receptor positive breast Cancer. However, the limited activity, toxicity and the development of resistance raised the current need for new potent nontoxic antiestrogen. Six novel TAM analogues 5a-f were synthesized using McMurry olefination reaction. Replacement of the dimethylamino group in TAM by piperidino, piperazino or N-methyl piperazino, substituting the phenyl ring with florine atom at p-position and changing the ethyl group by methyl, afforded compounds showing comparable activity to TAM (1). Compounds 5c and 5e showed significant increase in antiproliferative activity in two breast Cancer cell lines (MCF-7 and MDA-MB-231) compared to tamoxifen, while Other compounds showed similar activity. The increased Anticancer activity of compounds 5c and 5e was attributed to their ability to induce ER-independent cell death.

Keywords
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide; Breast cancer; DMEM/F12; Dulbecco’s modified Eagle medium nutrient mixture F-12; ER; Estrogen receptors; FBS; MOE; MTT; TAM; Tamoxifen analogues; Triaryl (Z)-olefins; estrogen receptor; fetal bovine serum; molecular operating environment; tamoxifen.