Molecular Docking, Synthesis, Characterization, and Preliminary Cytotoxic evaluation of new 1, 3, 4-Thiadiazole Derivatives as Αlpha-Estrogen Receptor Modulator

Abstract

Objective: This study concluded that these newly synthesized analogs may be represented as an exploitable source of new anticancer agents to fight breast cancer Methods: Using The crystal structure of Human α Estrogen Receptor (α-ER) with a 4-HYDROXYTAMOXIFEN(standard) as a co-crystalized ligand was gained from the protein data-bank (PDB code 3ERT) as a result of docking the 1,3,4-thiadiazole derivatives compounds(M1-M3) give good docking scores compared to the standard. Compounds M1-M3 was synthesized by multistep procedures from the reaction of intermediate (benzyloxy)phenyl)-1,3,4-thiadiazole-2(3H)-thione derivatives (D1, D2) and the 4-bromo-1-(cyclic amine1-yl)butan-1-one derivatives intermediate (A1, A2). The chemical structures of the target compounds and their intermediates were confirmed by FT-IR, 1H NMR, and 13C NMR. Results: The in-vitro cytotoxicity assay (MTT assay) demonstrated that compounds M1-M3 showed good inhibition ratios in Breast cancer cell line (MCF-7) comparable with drug control Tamoxifen Conclusion: From the docking study, it was concluded that piperidine and methyl-piperazine moiety were very successful to bind tightly to alpha estrogen receptors by making numerous interaction modes.