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

• Main Authors: Leow, Min Li, Chin, Christina Hui Li, Yu, Peggy Shuang, Pasunooti, Kalyan Kumar, Tay, Raymond Xu Zhan, Zhang, Dawei, Yoon, Ho Sup, Liu, Xue-Wei
• Other Authors: School of Physical and Mathematical Sciences
• Format: Article
• Language: English
• Published: 2013
• Subjects: DRNTU::Science::Chemistry::Biochemistry
• Online Access: https://hdl.handle.net/10356/99750; http://hdl.handle.net/10220/17385
• Institution: Nanyang Technological University

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.