Integration of Molecular Docking Approaches with Experimental Synthesis: Evaluation of Novel 1,4-Dihydropyridine derivatives for Antihypertensive activity

Hypertension affects a significant fraction of the global population and is widespread global health concern. Medical professionals frequently prescribe Calcium channel blockers as primary treatment for hypertension, due to its demonstrated efficacy and 1,4-dihydropyridine and it’s derivatives which are currently in use. The objective is to study antihypertensive effect of various analogues of 1,4-dihydropyridine derivatives with in-silico method of evaluation, synthesis and characterization. Ten derivatives were designed and docked on L-type calcium channel protein (PDB ID- 3LV3) using Autodock 1.5.7 and Biovia Discovery studio visualizer. The 5 derivatives of best binding energy were synthesized using Hantzsch method followed by characterization using IR, 1H NMR and MASS and assessments of antihypertensive activity pharmacologically by tail-cuff method using Nifedipine as standard drug. 1,4-dihydropyridine derivatives (DHP-01 to DHP-05) were synthesized and characterized. Nevertheless, a significant difference in lowering blood pressure was observed after comparing with standard nifedipine. The synthesized derivative DHP-02 was found to be effective as antihypertensive agent. Newly synthesized 1,4-dihydropyridine derivatives can be further studied for antihypertensive activity.