Benzofuran-Based Estrogen Receptor α Modulators as Anti-Cancer Therapeutics: In Silico and Experimental Studies

Min   Li   Leow; Hui Li   Christina   Chin; Peggy   Shuang   Yu; Kalyan   Kumar   Pasunooti; Raymond Xu   Zhan   Tay; Dawei      Zhang; Ho   Sup   Yoon; Xue-Wei      Liu

Abstract

In the search for new estrogen receptor alpha (ERα) modulators, a trial molecular screening was conducted and 5,6-dihydroxybenzofuran was identified as a possible drug target for ERα. The target molecular modelling molecule 1 and a series of 5,6-dihydroxybenzofurans have been synthesized and evaluated for their anti-proliferation activities against MCF-7 and MDA-MB-231 cells. From the SAR studies, potential functional groups have been identified, the two hydroxyl groups at C-5 and C-6 and the phenyl ring at C-2, which showed considerable cytotoxicity in MCF-7 breast cancer cells. In addition, the apoptotic abilities of the compounds have been measured in both MCF-7 ER(+) and MDA-MB-231 ER(-) breast cancer cells. The results demonstrated that our compounds inhibit MCF-7 breast cancer cells via ER(+). These preliminary results provide valuable information towards the identification of important functional groups present on 5,6-dihydroxybenzofuran, which could be a promising scaffold for designing novel ER ligands.

Keywords: Estrogen receptor, benzofuran, structure-activity relationships, proliferation, apoptosis.

« Previous