Novel hybrid molecules based on triazole-quinoline as potential anticancer agents: screening on MCF-7 cell line, docking studies, and pharmacokinetics evaluation

A novel series of quinoline-based 1,2,3-triazole hybrids were developed by copper-catalyzed 1,3-dipolar cycloaddition reactions of terminal alkyne appended to quinoline and aromatic/aliphatic azides individually. Structure of all the newly synthesized molecules was analyzed and confirmed based on H-1-NMR, C-13-NMR and HRMS data. Cytotoxicity of all molecules was evaluated against MCF-7 cell line by MTT assay in various mu M concentrations. The activity of a few compounds of this series is comparable to that of marketed drug Cisplatin. All the molecules showed good to moderate activity. The 2-chloro (7a) and 4-chloro (7b) substituted analogs showed excellent activity with IC50 values of 7.46 and 6.45 mu M, respectively, and the t-butyloxycarbonyl containing azetidine and pyperizine-substituted analogs showed moderate activity compared to Cisplatin. The Molecular docking performed against human estrogen receptor alpha ligand-binding domain and in-silico evaluation of pharmacokinetics are in favor to the experimental data. [GRAPHICS]