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

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

Volume: 20 Issue: 22

Author(s): Min Li Leow, Hui Li Christina Chin, Peggy Shuang Yu, Kalyan Kumar Pasunooti, Raymond Xu Zhan Tay, Dawei Zhang, Ho Sup Yoon and Xue-Wei Liu

Affiliation:

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

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.

Cite this article as:

Leow Li Min, Chin Christina Hui Li, Yu Shuang Peggy, Pasunooti Kumar Kalyan, Tay Zhan Raymond Xu, Zhang Dawei, Yoon Sup Ho and Liu Xue-Wei, Benzofuran-Based Estrogen Receptor α Modulators as Anti-Cancer Therapeutics: In Silico and Experimental Studies, Current Medicinal Chemistry 2013; 20 (22) . https://dx.doi.org/10.2174/0929867311320220007