Quantitative structure–activity relationship in aziridinyl-1,4-naphthoquinone antimalarials: study of theoretical correlations by the PM3 method Original Research Article

Several molecular parameters for 2,3,5-substituted 1,4-naphthoquinones including 2-aziridinyl and 2,3-aziridinyl-1,4-naphthoquinones with antimalarial activities were obtained with the semi-empirical PM3 method. The descriptor related to the Gibbs free energy of an isodesmic equation defining the reduction of the naphthoquinones was found to have high correlation with activity. The quantitative models reported clearly show a dependence of activity on the redox potential for reduction of the naphthoquinones. Compounds with lower values of ΔG for reduction are more active than those with higher values of ΔG.