فهرست نشریات علمی دسترسی آزاد ایران

Benzimidazole scaffolds are biologically and therapeutically useful chemical motifs against several diseases. Several derivatives are already known for benzimidazole, one of the most important derivatives known is 2-mercaptobenzimidazole with numerous biological activities were reported viz. antimicrobial, antiviral, anti-tumor and anti-inflammatory. Thus, several 2-mercaptobenzimidazole derivatives were designed and directly prepared through S-alkylation with four different para-substituted 1-bromomethyl benzene and N-alkylation with 1-(2-chloroethyl)piperidine, 1-(2-chloroethyl)-4-methylpiperazine and 1-(2-chloroethyl)-4-morpholine moieties with potential cytotoxic activities against breast cancer. Prior to the synthesis of the target compounds, docking studies were conducted which showed good docking scores compared to the standard raloxifene against estrogen receptor alpha (ERα), which is considered one of the main molecular targets in breast cancer pathogenesis. The synthesis of the target compounds 14 a-d was successful, and their structures were confirmed with FT-IR, 1H NMR, 13C NMR, and ESI-MS analysis. The in-vitro cytotoxicity assay (MTT assay) demonstrated that compound 14c possesses excellent cytotoxic effects towards breast cancer cell line (MDA-MB-231: IC50: 24.78± 1.02 µM), compared to standard raloxifene with an IC50: 26.73 µM. From the docking study, it was concluded that piperidine, methyl-piperazine and morpholine moiety successfully bind tightly to alpha estrogen receptors by making numerous interaction modes.