STRUCTURE-ACTIVITY RELATIONSHIP FOR SOME 2',3'-DIDEOXYNUCLEOSIDE ANTI-HIV DRUGS USING MOLECULAR ELECTROSTATIC POTENTIAL MAPPING

Molecular electrostatic potential(MEP) maps of azido thymidine (AZT), some of its analogs and derivatives and certain other 2',3'-dideoxy nu cleosides having different anti-HIV activities have been studied. The optimised hybridization displacement charges (I-IDC) combined with MND O Lowdin charges, continuosly distributed in three dimension spherical ly symmetrically as a Slater cloud at each site were used to compute t he MEP maps. The negative MEP region near the O5' sites of these molec ules appears to be of primary importance from the point of view of the ir anti-HIV activity. The roles of the azido group in AZT and fluorine atoms substituted at different positions in the sugar moiety have bee n evaluated. The azido group in AZT behaves as a strongly electronegat ive group.