Theoretical study of relation between electronic structure and antiplasmodial activity of chalcone derivatives

Abstract

Malaria is a parasitic disease that is widespread in the world and endemic to intertropical zones. According to World Health Organization, Africa is the most affected by malaria, especially in its sub-Saharan zone. Important work has been done on malaria, however, there are some drug resistance developed by certain strains of plasmodium. This work aim to propose a model of antimalarial 2D-pharmacophore based on a theoretical study of the relation between the electronic structure of a series of molecules derived from chalcone and the antiplasmodial activity in vitro against the pf3D7 strain. This QSAR study was done according to the Klopman-Peradejordi-Gὀmez technique (KPG). Using the Gaussian program, the DFT / B3LYP method in the 6-31G database (d, p), the optimization of the geometries of the molecules was done. After a multiple linear regression using Statistica software, an equation expressing log (IC50) as a function of eight molecular reactivity indices was obtained. Analysis of the results made it possible to propose a 2D pharmacophore; this will enable us to propose more reactive antimalarial molecules. The process seems to be charge and orbital-controlled.