title: Analysis of binding parameters of HIV-1 integrase inhibitors: correlates of drug inhibition and resistance.
abstract: This study undertook an exploratory data analysis of the binding parameters of HIV-1 integrase inhibitors. The study group involved inhibitors in preclinical development from the diketo acid, pyrroloquinoline and naphthyridine carboxamide families and the most advanced inhibitors Raltegravir and Elvitegravir. Distinct differences were observed in the energetics of binding between the studied classes of inhibitors that also correlated with drug resistant patterns. Quantitative-property-activity-relationships correlated experimental IC(50) values to the binding energy and the logarithm of the partition coefficient between n-octanol and water (clogP). The approach followed here serves as an improved basis for the development of 'second generation' integrase inhibitors.
authors.affiliation: Department of Biological Sciences, University of Cyprus, Nicosia, Cyprus. eloizido@ucy.ac.cy
authors.forename: Eriketi Z
authors.initials: EZ
authors.lastname: Loizidou
authors.forename: Constantinos D
authors.initials: CD
authors.lastname: Zeinalipour-Yazdi
authors.forename: Tasos
authors.initials: T
authors.lastname: Christofides
authors.forename: Leondios G
authors.initials: LG
authors.lastname: Kostrikis
mesh_terms: D024882:Drug Resistance, Viral / Q000187:drug effects*; D019427:HIV Integrase / Q000737:chemistry* / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000201:enzymology*; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D011487:Protein Conformation; D021281:Quantitative Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D019428:HIV Integrase Inhibitors; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1