title: Prediction of HIV-1 protease inhibitory activity of 4-hydroxy-5,6-dihydropyran-2-ones: QSAR study.
abstract: Inhibition of human immunodeficiency virus 1 (HIV-1) protease is an important strategy for the treatment of HIV and acquired immune deficiency syndrome (AIDS). Therefore, HIV-1 protease inhibitory activity of dihydropyranone derivatives has been analyzed with different physico-chemical parameters. In the present work, QSAR studies were performed on a series of 4-hydroxy-5,6-dihydropyran-2-ones to explore the physico-chemical parameters responsible for their HIV-1 protease inhibitory activity. Physico-chemical parameters were calculated using WIN CAChe 6.1. Stepwise multiple linear regression analysis was performed to derive QSAR models which were further evaluated for statistical significance and predictive power by internal and external validation. The selected best QSAR model was having correlation coefficient (R) = 0.875 and cross-validated squared correlation coefficient (Q²) = 0.707. The developed significant QSAR model indicates that hydrophobicity of whole molecule and the substituent present at sixth position of dihydropyranones play an important role in the HIV-1 protease inhibitory activities of 4-hydroxy-5,6-dihydropyran-2-ones.
authors.affiliation: Pharmaceutical Chemistry Research Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar, Madhya Pradesh, India.
authors.forename: V
authors.initials: V
authors.lastname: Ravichandran
authors.forename: V K
authors.initials: VK
authors.lastname: Mourya
authors.forename: R K
authors.initials: RK
authors.lastname: Agrawal
mesh_terms: D004789:Enzyme Activation / Q000187:drug effects*; D016333:HIV Protease / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011753:Pyrones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D011480:Protease Inhibitors; D011753:Pyrones; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1