Synthesis, Vibrational Analysis, Electronic Structure Property Investigation and Molecular Simulation of Sulphonamide‐Based Carboxamides against <i>Plasmodium</i> Species

Abstract

Abstract Carboxamide derivatives containing p‐ toluenesulfonamide functionality were synthesized by the environmentally friendly method using zinc chloride catalyst. All the synthesized compounds; 2‐ N ‐(4‐methylbenzenesulfonyl)‐1‐phenylformamido‐ N ‐(4‐nitrophenyl) acetamide (MBPNA), 2‐ N ‐(4‐methylbenzenesulfonyl)‐1‐phenylformamido‐ N ‐(4‐nitrophenyl)‐3‐phenyl propanamide (MBPNPP), 3‐(1 H ‐indol‐2‐yl)‐2‐ N ‐(4‐methylbenzenesulfonyl)‐1‐phenylformamido‐ N ‐(4‐nitrophenyl) propanamide (HIMBPNP) and 4‐Methyl‐2‐ N ‐(4‐methylbenzenesulfonyl)‐1‐phenylformamido‐ N ‐(4‐nitrophenyl) pentanamide (MBPNP) were characterized by FT‐IR, 1 H and 13 C NMR studies. Density functional theory (DFT) investigations using the B3LYP/6‐311++G (d, p) functional/basis set along with molecular docking simulations were conducted to explore their electronic structure, reactivity indexes and bioactive potentials respectively. The results of the molecular anti‐plasmodal simulation showed that the compounds are very effective drug candidates especially HIMBPNP which among them contains the Indol group. The result of the present research therefore requires further attention as it provides a suitable platform for the discovery and biological assessment of new anti‐malaria drugs.