Extended Rule of Five and Prediction of Biological Activity of Peptidic HIV-1-PR Inhibitors

In this research work, we have applied "Lipinski's RO5" for pharmacokinetics (PK) study and to predict the activity of peptidic HIV-1 protease inhibitors. Peptidic HIV-1-PRIs have been taken from literature with their observed biological activities (OBAs) in term of IC50. The logarithms of the inverse of IC50 have been used as biological end point o(log1/C) in the study. For calculation of physicochemical parameters, the molecular modeling and geometry optimization of all the derivatives have been carried out with CAChe Pro software using semiempirical PM3 method. Prediction of the biological activity of the inhibitors has shown that the best QSAR model is constructed from pharmacokinetic properties, molecular weight and hydrogen bond acceptor. This also proved that these properties play important role to describe the PKs of the drugs. On the basis of the derived models one can build up a theoretical basis to access the biological activity of the compounds of the same series.