title: A quantitative structure-activity relationship study on some HIV-1 protease inhibitors using molecular connectivity index.
abstract: A quantitative structure-activity relationship (QSAR) study has been made on two different series of tetrahydropyrimidinones acting as HIV-1 protease inhibitors. A structural parameter, the first order valence molecular connectivity index ((1)chi(v)), has been used to account for the variation in the activity. The protease inhibition activity as well as the antiviral potency of the compounds are found to be significantly correlated with (1)chi(v) of P(2)/P(2') substituents attached to the two nitrogens N1 and N3, suggesting that substituents containing less electronegative and more saturated atoms, meaning thereby the less polar or more hydrophobic substituents, will be more advantageous. Further, if P(2) and P(2') are dissimilar, the former is found to be more effective than the latter. This difference is attributed to a conformational change in the enzyme that may be more favorable to P(2) binding than to P(2') binding.
authors.affiliation: Department of Chemistry, Birla Institute of Technology and Science, 333 031, Pilani, India.
authors.forename: P
authors.initials: P
authors.lastname: Gayathri
authors.forename: V
authors.initials: V
authors.lastname: Pande
authors.forename: R
authors.initials: R
authors.lastname: Sivakumar
authors.forename: S P
authors.initials: SP
authors.lastname: Gupta
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry*; D016333:HIV Protease / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D011487:Protein Conformation / Q000187:drug effects; D011744:Pyrimidinones / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D011480:Protease Inhibitors; D011744:Pyrimidinones; D016333:HIV Protease