Research Article
Tetrahydroxy Cyclic Urea-Potent Inhibitor for HIV-1 Protease Wild Type and Mutant Type- A Computational Design
S. SREE KANTH and M. VIJJULATHA
ABSTRACT
A series of novel tetrahydroxy cyclic urea molecules as HIV-1 protease inhibitors were designed using computational techniques. The designed molecules were compared with the known cyclic urea molecules by performing docking studies on six of wild type protein and three mutant protein varieties and calculating their ADME properties. A series of novel molecules were designed by substituting hydrogen at the P1/ P1' positions with hydroxyl group increasing the bioavailability these had better ADME properties and binding affinity towards HIV-1 protease. The biological activity of these inhibitors were predicted by a model equation generated by the regression analysis between biological activity (log 1/Ki) of known inhibitors and there combined docking scores from six of the wild type protein docking. The synthetic studies are in progress
Received 7 November 2007; Accepted 5 January 2008