title: Docking-based 3D-QSAR analyses of pyrazole derivatives as HIV-1 non-nucleoside reverse transcriptase inhibitors.
abstract: 1,3,4,5-tetrasubstituted-pyrazoles (TPs) have been recently identified as a new class of potent non-nucleoside HIV-1 reverse transcriptase (RT) inhibitors. A computational strategy based on molecular docking studies, followed by docking-based comparative molecular fields analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA), has been used to elucidate the atomic details of the RT/TP interactions and to identify the most important features impacting the TP antiretroviral activity. The final CoMSIA model resulted to be the more predictive, showing r (ncv) (2)  = 0.97, r (cv) (2)  = 0.723, SEE = 0.248, F = 240.291, and r(2) (pred) = 0.77. The results allowed us to obtain useful information for the design of new compounds with improved potency toward WT HIV-1 and also against clinically relevant resistant mutants.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Genova, Viale Benedetto XV n.3, 16132 Genova, Italy. cichero@unige.it
authors.forename: Elena
authors.initials: E
authors.lastname: Cichero
authors.forename: Paola
authors.initials: P
authors.lastname: Fossa
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D003198:Computer Simulation; D017076:Computer-Aided Design; D015658:HIV Infections / Q000188:drug therapy; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011720:Pyrazoles / Q000737:chemistry; D021281:Quantitative Structure-Activity Relationship; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D011720:Pyrazoles; D018894:Reverse Transcriptase Inhibitors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase