A quantum-chemical study of the relationships between electronic structure and anti-HIV-1 activity of a series of HEPT derivatives

Gaston A. Kpotin, Guy S. Atoho

Abstract

A study of the relationships between electronic structure and anti HIV-1 activities of a series of 1-[2-hydroxyéthoxyméthyl]- 6-(phenylthio) thymine (HEPT) derivatives was carried out. The electronic structure was obtained at the B3LYP/6-311G(d,p) level after full geometry optimization. A linear multiple regression analysis was performed with the anti HIV activity as the dependent variable and a set of reactivity indices belonging to the atoms of a common skeleton as independent variables. A statistically significant equation (R= 0.98, R²= 0.95, adj-R²= 0.94, F(6,14)=49.02, p<0.00000 and SD=0.28) was obtained. The process seems to be charge and orbital-controlled. Based on the analysis of the results, a partial two-dimensional anti HIV-1 pharmacophore is proposed.