Benzofuran-based estrogen receptor α modulators as anti-cancer therapeutics: in silico and experimental studies

• Published in: Current medicinal chemistry Vol. 20; no. 22; p. 2820
• Main Authors: Leow, Min Li, Chin, Hui Li Christina, Yu, Peggy Shuang, Pasunooti, Kalyan Kumar, Tay, Raymond Xu Zhan, Zhang, Dawei, Yoon, Ho Sup, Liu, Xue-Wei
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01.07.2013
• Subjects: Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Benzofurans - pharmacology; Cell Line, Tumor; Cell Survival - drug effects; Computer Simulation; Estrogen Receptor alpha - metabolism; Estrogen Receptor Modulators - pharmacology; Humans; Models, Molecular
• ISSN: 1875-533X
• DOI: 10.2174/0929867311320220007

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.