A quantitative structure–activity relationship study on some HIV-1 protease inhibitors using molecular connectivity index Original Research Article

A quantitative structure–activity relationship (QSAR) study has been made on two different series of tetrahydropyrimidinones acting as HIV-1 protease inhibitors. A structural parameter, the first order valence molecular connectivity index (1χv), has been used to account for the variation in the activity. The protease inhibition activity as well as the antiviral potency of the compounds are found to be significantly correlated with 1χv of P2/P2′ substituents attached to the two nitrogens N1 and N3, suggesting that substituents containing less electronegative and more saturated atoms, meaning thereby the less polar or more hydrophobic substituents, will be more advantageous. Further, if P2 and P2′ are dissimilar, the former is found to be more effective than the latter. This difference is attributed to a conformational change in the enzyme that may be more favorable to P2 binding than to P2′ binding.