Acquired Immunodeficiency Syndrome (AIDS) is one of the most fatal disorders for which no completely successful chemotherapy has been developed so far. Human Immunodeficiency Virus (HIV), a retrovirus, is responsible for inducing AIDS. Protease enzyme encoded by HIV-1 is one of the major targets for the development of new chemotherapeutic agents. To expedite the search for a suitable more potent anti-HIV-1 inhibitor, we propose to conduct a detailed Quantitative Structure-Activity Relationship (QSAR) study of anti-HIV-1 protease inhibitors. We plan to develop QSAR models for HIV-1 protease inhibitors synthesized so far. Since the presence of a hydrophobic channel at the binding site of protease enzyme is well established, the in-depth study of the role of hydrophobicity of substituents of the ligands in the inhibition of the enzyme will be conducted. We will also carry out the lateral validation of our models using Comparative QSAR. This study will provide important lead(s) for the development of more potent anti-HIV-1 drugs with lesser side effects.
| Reddy, A Srinivas; Kumar, Sunil; Garg, Rajni (2010) Hybrid-genetic algorithm based descriptor optimization and QSAR models for predicting the biological activity of Tipranavir analogs for HIV protease inhibition. J Mol Graph Model 28:852-62 |
| Garg, Rajni; Bhhatarai, Barun (2008) Possible allosteric interactions of monoindazole-substituted P2 cyclic urea analogues with wild-type and mutant HIV-1 protease. J Comput Aided Mol Des 22:737-45 |
| Garg, Rajni; Patel, Disha (2005) Hydrophobicity in the design of P2/P2' tetrahydropyrimidinone HIV protease inhibitors. Bioorg Med Chem Lett 15:3767-70 |
| Bhhatarai, Barun; Garg, Rajni (2005) From SAR to comparative QSAR: role of hydrophobicity in the design of 4-hydroxy-5,6-dihydropyran-2-ones HIV-1 protease inhibitors. Bioorg Med Chem 13:4078-84 |
| Garg, Rajni; Bhhatarai, Barun (2004) A mechanistic study of 3-aminoindazole cyclic urea HIV-1 protease inhibitors using comparative QSAR. Bioorg Med Chem 12:5819-31 |
