Design and synthesis of novel β-diketo derivatives as HIV-1 integrase inhibitors.
ABSTRACT A series of novel β-diketo derivatives which combined the virtues of 1,3-diketo, 1,2,3-triazole and polyhydroxylated aromatics moieties, were designed and synthesized as potential HIV-1 integrase (IN) inhibitors and evaluated their inhibition to the strand transfer process of HIV-1 integrase. The result indicates that 3,4,5-trihydroxylated aromatic derivatives exhibit good inhibition to HIV-1 integrase, but dihydroxylated aromatic derivatives and corresponding methoxy aromatic derivatives appear little inhibition to HIV-1 integrase.
- SourceAvailable from: Dr. Pawan K. Gupta[Show abstract] [Hide abstract]
ABSTRACT: A QSAR study was performed on curcumine derivatives as HIV-1 integrase inhibitors using multiple linear regression. The statistically significant model was developed with squared correlation coefficients (r2) 0.891 and cross validated r2 (r2cv) 0.825. The developed model revealed that electronic, shape, size, geometry, substitution's information and hydrophilicity was important atomic properties for determining the inhibitory activity of these molecules. The model was also tested successfully for external validation (r2pred = 0.849) as well as Tropsha's test for model predictability. Furthermore, the domain analysis was carried out to evaluate the prediction reliability of external set molecules model. The model was statistically robust and had good predictive power which can be successfully utilized for screening of new molecules.Current Computer - Aided Drug Design 11/2012; · 1.54 Impact Factor