QSAR Analysis of Chicoric Acid Derivatives as HIV–1 Integrase Inhibitors

Kamlesh K. Sahu,a V. Ravichandran,b Prateek K. Jain,b Simant Sharma,b V. K. Mouryac and R. K. Agrawalb*

a Department of Applied Chemistry, Tohoku University Graduate School of Engineering Aoba–yama, Sendai, JAPAN.
b Department of Pharmaceutical Sciences, Dr. H. S. Gour University, Sagar (M.P.), 470 003 India.
c Govt. College of Pharmacy, Osmanpura, Aurangabad, Maharashtra, India.
* Corresponding author: Phone No. 07582233934, E–mail: dragrawal2001@yahoo.co.in

HIV-1 Integrase is a potential target for anti- HIV therapy. It is an essential enzyme required for replication of the AIDSvirus. Chicoric acid derivatives act against HIV integrase and thus have the potential to become a part of anti-HIV drug regime. Chicoric acid derivatives have all the features required for it to act as good anti–HIV agent like poly aromatic rings and a central linker. In present study, we have carried out QSAR study of Chicoric acid derivatives using the software WIN CAChe 6.1 and STATISTICA in order to improve its activity. Multiple linear regression analysis was performed to derive QSAR models which were further evaluated for statistical significance and predictive power by internal and external validation. The predictive ability of the selected model was also confirmed by leave 25% out cross validation. The QSAR model indicates that heat of formation, partition coefficient, lowest unoccupied molecular orbital, solvent accessible surface area and shape index play an important role for the HIV integrase inhibitory activities. The results of the present study may be useful on the designing of more potent chicoric acid analogues as HIV integrase inhibitory agents.

Keywords: Human immunodeficiency virus, integrase; inhibition; quantitative structure activity relationship; chicoric