Pharmacophore modelling and atom-based 3D-QSAR studies on N-methyl pyrimidones as HIV-1 integrase inhibitors |
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Authors: | Reddy Karnati Konda Singh Sanjeev Kumar Dessalew Nigus Tripathi Sunil Kumar Selvaraj Chandrabose |
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Affiliation: | Department of Bioinformatics, Alagappa University, Karaikudi, Tamil Nadu, India. |
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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 (Q(2)?=?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. |
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