Pharmacophore modelling and atom-based 3D-QSAR studies on N-methyl pyrimidones as HIV-1 integrase inhibitors

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 (r² = 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.

Keywords::

• 3D-QSAR
• AIDS
• HIV-1 IN
• N-methyl pyrimidones
• pharmacophore modelling

Acknowledgements

The authors thank M. Ravikumar for the detailed discussion and suggestions. The authors thank an anonymous referee for the valuable suggestion.

Declaration of interest

The authors report no declarations of interest.