title: 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 (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.
authors.affiliation: Department of Bioinformatics, Alagappa University, Karaikudi, Tamil Nadu, India.
authors.forename: Karnati Konda
authors.initials: KK
authors.lastname: Reddy
authors.forename: Sanjeev Kumar
authors.initials: SK
authors.lastname: Singh
authors.forename: Nigus
authors.initials: N
authors.lastname: Dessalew
authors.forename: Sunil Kumar
authors.initials: SK
authors.lastname: Tripathi
authors.forename: Chandrabose
authors.initials: C
authors.lastname: Selvaraj
mesh_terms: D004305:Dose-Response Relationship, Drug; D019427:HIV Integrase / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D013329:Structure-Activity Relationship
chemical_list: D019428:HIV Integrase Inhibitors; D011744:Pyrimidinones; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1