2D-Qsar Modeling of the Anti-Malarial Activity Prediction of 4-Quinolinylhydrazone Derivatives on Strain K1
Micheline Panewai
Laboratory of Chemical Physics-Materials and Molecular Modeling (LCP3M), Faculté de Sciences et Techniques, Université d’Abomey-calavi, 03 BP 3409 Cotonou, Rep., Benin.
Gautier Sèlonou Kankinou
Laboratory of Chemical Physics-Materials and Molecular Modeling (LCP3M), Faculté de Sciences et Techniques, Université d’Abomey-calavi, 03 BP 3409 Cotonou, Rep., Benin.
Simplice Koudjina
Laboratory of Chemical Physics-Materials and Molecular Modeling (LCP3M), Faculté de Sciences et Techniques, Université d’Abomey-calavi, 03 BP 3409 Cotonou, Rep., Benin and National High School of Applied Biosciences and Biotechnologies (ENSBBA), National University of Science, Technology, Engineering and Mathematics (UNSTIM), BP 2282 Goho Abomey, Rep., Benin.
Gaston Assongba Kpotin *
Laboratory of Chemical Physics-Materials and Molecular Modeling (LCP3M), Faculté de Sciences et Techniques, Université d’Abomey-calavi, 03 BP 3409 Cotonou, Rep., Benin.
*Author to whom correspondence should be addressed.
Abstract
Malaria is a serious health problem in Africa and other poor regions of the world, where new anti-malarial drugs are urgently needed at a price affordable to all. This theoretical study on the relationship between the electronic structure and the anti-malarial activity of a series of 4-quinolinylhydrazone derivatives on a chloroquine-resistant strain (K1) is carried out with the aim of proposing new molecules capable of curatively combating malaria. The QSAR study was carried out using the Klopman-Peradejordi-Gómez (KPG) technique. This enabled us to express the logarithm of the median inhibitory concentration as a function of certain local atomic reactivity indices of certain atoms in the common skeleton of this series of 4-quinolinylhydrazone derivatives. Calculations were performed using the B3LYP hybrid functional of the DFT method in the 6-31G (d, p) extended basis implemented in the Gaussian program. Statistica 10 software was used to obtain the multiple linear regression equation. A statistically acceptable equation was obtained for the studied serie. Analysis of this equation led to the proposal of a 2D pharmacophore for anti-malarial activity. From this 2D pharmacophore we proposed hypothetical molecules and among these proposed compounds, four molecules showed good biological activity after log(IC50) calculation.
Keywords: Anti-malarial activity, Quinolinylhydrazone derivatives, QSAR, DFT