Synthesis and Biological Evaluation of the Salicylamide and Salicylic Acid Derivatives as Anti-Estrogen Agents

Yasemin      Dundar; Yasemin      Ozatik; Orhan      Ozatik; Volkan      Ergin; Tijen      Onkol; Adnan      Menevse; Kevser      Erol; M.      Fethi Sahin

doi:10.2174/1573406411208030481

Abstract

Alkylphenols have xenoestrogenic activity, which mimic the action of physiological estrogens and these mimicking activities are mainly mediated by nongenomic pathway. Nongenomic pathway plays a pivotal role in breast, endometrial and ovarian cancers’ growth and development. In this study, various alkylphenol derivatives were prepared and screened for their anti-uterotrophic and uterotrophic activity. Among these compounds, 2-hydroxy-5-nonanoylbenzamide (compound 1b) showed 93.99% inhibitory activity in the anti-uterotrophic test performed, and was found inactive in the uterotrophic activity test. Moreover, all test compounds were examined for the effect on uterine histopathological changes, and plasma 17β-estradiol (E2) level. Compound 1b was also tested for in vitro anti-cancer activity against ER+, human breast cancer cell line MCF-7, and it reduced cell viability to 74.01% at 50 nM concentration.

Keywords: Anti-breast cancer activity, anti-estrogenic activity, anti-uterotrophic activity, nongenomic response, pnonylphenol, xenoestrogens, Alkylphenols, xenoestrogenic activity, nonanoylbenzamide, β-estradiol