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.

A novel benzofuran derivative, ACDB, induces apoptosis of human chondrosarcoma cells through mitochondrial dysfunction and endoplasmic reticulum stress

“…Therefore, to explore a novel therapeutic agent targeting the malignant survival of chondrosarcoma would be crucial for ameliorating the prognosis of patients. Benzofuran derivative has recently been reported to show anticancer activity in breast and cervical cancer [32, 33]. However, the antitumor activity of benzofuran derivative in chondrosarcoma cells are mostly unknown.…”

Design, Molecular Modelling and Synthesis of Novel Benzothiazole Derivatives as BCL-2 inhibitors

“…Series 3, compounds (8a-f), was prepared though a similar pattern as compounds 7a-i, by the direct coupling of equimolar amounts of the carboxylic acid (10) and the respective amino compounds (Ia-f, Fig. 3) using EDC.HCl as coupling agent/ DMAP as a base in dry DMF under N 2 atmosphere [35]. Using the same coupling procedure [35], compound (6) and the respective amino compounds (IIa,b, Fig.…”

“…3) using EDC.HCl as coupling agent/ DMAP as a base in dry DMF under N 2 atmosphere [35]. Using the same coupling procedure [35], compound (6) and the respective amino compounds (IIa,b, Fig. 3) were reacted yielding 9a,b, series 5, Fig.…”

“…Compound 6 served as a crucial starting point for the synthesis of series 1, 3 and 5 (scheme 2). the titled compounds, series (7a-i) were prepared by direct coupling of equimolar amounts of the carboxylic acid (6) and the respective substituted piperazine in presence of EDC.HCl as coupling agent/ DMAP as a base in dry DMF under N 2 atmosphere [35]. Series 3, compounds (8a-f), was prepared though a similar pattern as compounds 7a-i, by the direct coupling of equimolar amounts of the carboxylic acid (10) and the respective amino compounds (Ia-f, Fig.…”

“…Compound (10) was prepared upon reaction of 3-nitro-4-(phenethylamino)benzoic acid (3), which was obtained in good yields (94%) and purity according to Fig. 5, and ethyl 2-amino benzo[d]thiazole-6carboxylate (4) [35]. The titled compound (10) was subjected to ester hydrolysis to yield compound (11).…”