Synthesis, molecular docking, antiplasmodial and antioxidant activities of new sulfonamido-pepetide derivatives

Abstract

Twenty-three new series of toluene-sulfonamide dipeptide derivatives were synthesized and screened for antiplasmodial and antioxidant potencies. Many of the derivatives were active against Plasmodium falciparum with IC50 ranging from 3.20 – 9.10 μM. The ability of compounds 7h, 7m and 7n (IC50 of 7.53, 7.21 and 6.01 μg/mL respectively) to scavenge DPPH free radicals were comparable to that of ascorbic acid. Additionally, molecular docking disclosed that four compounds exhibited theoretical inhibition constant at submicromolar concentrations (Ki = 0.72, 0.75, 0.57, and 0.53 μM respectively) compare to the reference ligand (a pyrazole sulfonamide; Ki = 0.01 μM). Overall, some of the derivatives possess antimalarial property as well as the ability to inhibit oxidative stress in malaria pathophysiology; and hence, are good candidates for further antimalarial drug research.

Keywords

• Organic chemistry
• Pharmaceutical chemistry
• Synthesis
• Dipeptides
• Sulphonamides
• Antimalarial