1. Pharmacophore modelling and atom-based 3D-QSAR studies on N-methyl pyrimidones as HIV-1 integrase inhibitors.
- Author
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Reddy, Karnati Konda, Singh, Sanjeev Kumar, Dessalew, Nigus, Tripathi, Sunil Kumar, and Selvaraj, Chandrabose
- Subjects
QSAR models ,INTEGRASE inhibitors ,HYDROGEN bonding ,HIV ,LIGANDS (Biochemistry) ,MOLECULAR association ,DIHYDROGEN bonding - Abstract
Pharmacophore modelling and atom-based 3D-QSAR studies were carried out for a series of compounds belonging to N-methyl pyrimidones as HIV-1 integrase inhibitors. Based on the ligand-based pharmacophore model, we got 5-point pharmacophore model AADDR, with two hydrogen bond acceptors (A), two hydrogen bond donors (D) and one aromatic ring (R). The generated pharmacophore-based alignment was used to derive a predictive atom-based 3D-QSAR model for the training set ( r
2 == 0.92, SD == 0.16, F == 84.8, N == 40) and for test set ( Q2 == 0.71, RMSE == 0.06, Pearson R == 0.90, N == 10). From these results, AADDR pharmacophore feature was selected as best common pharmacophore hypothesis, and atom-based 3D-QSAR results also support the outcome by means of favourable and unfavourable regions of hydrophobic and electron-withdrawing groups for the most potent compound 30. These results can be useful for further design of new and potent HIV-1 IN inhibitors. [ABSTRACT FROM AUTHOR]- Published
- 2012
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