A novel series of 1,4-disubstituted 1,2,3-triazole derivatives (3a-3m) were one pot synthesized via cupper nanoparticles azide-alkyne click chemistry, and evaluated for their lung cancer (A549), prostate cancer (PC-3) inhibitory activity. Meanwhile, the activity of compounds containing 1,2,3-triazoles was higher than that of reference compounds. Out of these all, compound 3a showed most notable anticancer activity against prostate cancer cell line with IC50 value of 8.08 μM and 16.18 μM in A549, respectively. In particular, hybrid compound 3f was found to be the most potent derivative with IC50 values of 15.46 μM against one strain lung cancer cell line and was found to be more selective against prostate cancer (PC-3). Further the compounds 3g, 3e and 3b has been moderate tested for its anticancer activity and its inhibitory activity against A549 and PC-3 cell lines. Furthermore 3c,3k was found to be non-toxic against cell lines when screened for toxicity. To elucidate the interaction mechanism between the active potential binding site of nitrate reductase protein and its inhibitor, the docking-based molecular dynamics simulation (MD) and lamarckian genetic algorithm (LGA) calculations was selected for freezing, default parameters used in autodock 4.2. In the present investigation we focused mainly on the binding energy, hydrogen bonds and distance between the protein and ligand. The results show that compound 3f was potently bound to TYR248, LYS273 with highest score -6.96.