title: Benzofuran-based estrogen receptor α modulators as anti-cancer therapeutics: in silico and experimental studies.
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.
authors.affiliation: Division of Chemical and Biological Chemistry, School of Physical and Mathematical Sciences, Nayang Technological University, 21 Nanyang Link, Singapore 637371, Singapore.
authors.forename: Min Li
authors.initials: ML
authors.lastname: Leow
authors.forename: Hui Li Christina
authors.initials: HL
authors.lastname: Chin
authors.forename: Peggy Shuang
authors.initials: PS
authors.lastname: Yu
authors.forename: Kalyan Kumar
authors.initials: KK
authors.lastname: Pasunooti
authors.forename: Raymond Xu Zhan
authors.initials: RX
authors.lastname: Tay
authors.forename: Dawei
authors.initials: D
authors.lastname: Zhang
authors.forename: Ho Sup
authors.initials: HS
authors.lastname: Yoon
authors.forename: Xue-Wei
authors.initials: XW
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001572:Benzofurans / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003198:Computer Simulation; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular
chemical_list: D000970:Antineoplastic Agents; D001572:Benzofurans; C506487:ESR1 protein, human; D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha