The College of Pharmacy discussed the PhD dissertation entitled “Design, Synthesis, and Preliminary Cytotoxicity Evaluation of New 2-Mercaptobenzimidazole Derivatives” by the student Shahbaa Shafeeq Rzoqi and the supervisor, Assistant Professor Dr. Mohammed Hassan Mohammed, at the Pharmaceutical Chemistry Department. The study aimed to conduct a molecular docking study and synthesize a new series of benzimidazole derivatives as possible alpha estrogen receptor inhibitors (by extracting their IC50 values) according to the SAR requirements. The study included the design of several 2-mercaptobenzimidazole derivatives that were directly prepared through S-alkylation with four different para-substituted 1-bromomethyl benzenes, followed by N-alkylation and ester hydrolysis, and o-alkylation with 1-(2-chloroethyl) piperidine, methylpiperazine, and 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). The results showed that the in-vitro cytotoxicity assay (MTT assay) demonstrated that compounds F1, F2, and F4 possess excellent cytotoxic effects (IC50: 30.61 ± 3.28µM, IC50: 13.43 ± 2.34µM, IC50: 24.78 ± 1.02µM, respectively) towards breast cancer cell lines compared to standard raloxifene with IC50: 26.73 ± 11.84µM. The study recommended to complete kinetic studies of compounds (F1, F2, F4, and F5) with further in vitro cytotoxic activity research on different cancer cell lines and in vivo studies.
