Molecular Modeling of Anti HIV Drugs of Protease Inhibitor Group by CoMFA

Abstract

An anti-HIV agent may exert its activity by inhibiting a variety of steps in the life cycle of virus. In recent advances medicinal chemists have focused their attention mainly on virial binding to target cells, virus-cell fusion, virus uncoating, reverse transcription of genomic RNA, viral integration, gene expression, cleavage events through protease inhibitors and virion mutarotation. In present study cleavage events through protease inhibitors have been done by CoMFA. There are a number of physical, structural and chemical descriptors which may be helpful in computer aided drug designing. Out of them hydrophobicity in particular can be easily quantified for complete molecule or even for individual substituent. 26 derivatives of cyclic urea and 8 derivatives of Isosteres belonging to non-peptidic and peptidic PR inhibitors were taken as study material and a number of MLR equations using different combinations of descriptors have been developed. On the basis of these regression values, theoretical activity of the various models is predicted which provides an insight into structural and binding features of the proposed models.