title: QSAR models for HEPT derivates as NNRTI inhibitors based on Monte Carlo method.
abstract: A series of 107 1-[(2-hydroxyethoxy)-methyl]-6-(phenylthio) thymine (HEPT) with anti-HIV-1 activity as a non-nucleoside reverse transcriptase inhibitor (NNRTI) has been studied. Monte Carlo method has been used as a tool to build up the quantitative structure-activity relationships (QSAR) for anti-HIV-1 activity. The QSAR models were calculated with the representation of the molecular structure by simplified molecular input-line entry system and by the molecular graph. Three various splits into training and test set were examined. Statistical quality of all build models is very good. Best calculated model had following statistical parameters: for training set r(2) = 0.8818, q(2) = 0.8774 and r(2) = 0.9360, q(2) = 0.9243 for test set. Structural indicators (alerts) for increase and decrease of the IC50 are defined. Using defined structural alerts computer aided design of new potential anti-HIV-1 HEPT derivates is presented.
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
authors.forename: Alla P
authors.initials: AP
authors.lastname: Toropova
authors.affiliation: IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Toropov
authors.affiliation: University of Niš, Faculty of Medicine, Department of Chemistry, Bulevar Dr Zorana Djindjića 81, 18000 Niš, Serbia.
authors.forename: Jovana B
authors.initials: JB
authors.lastname: Veselinović
authors.affiliation: University of Niš, Faculty of Medicine, Department of Chemistry, Bulevar Dr Zorana Djindjića 81, 18000 Niš, Serbia.
authors.forename: Filip N
authors.initials: FN
authors.lastname: Miljković
authors.affiliation: University of Niš, Faculty of Medicine, Department of Chemistry, Bulevar Dr Zorana Djindjića 81, 18000 Niš, Serbia. Electronic address: aveselinovic@medfak.ni.ac.rs.
authors.forename: Aleksandar M
authors.initials: AM
authors.lastname: Veselinović
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017076:Computer-Aided Design; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009010:Monte Carlo Method; D021281:Quantitative Structure-Activity Relationship; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013941:Thymine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; C061818:1-((2-hydroxyethoxy)methyl)-6-(phenylthio)thymine; D054303:HIV Reverse Transcriptase; D013941:Thymine
keywords: CORAL software; Computer-aided drug design; HEPT; Monte Carlo method; QSAR; SMILES