title: QSAR study and conformational analysis of 4-arylthiazolylhydrazones derived from 1-indanones with anti-Trypanosoma cruzi activity.
abstract: A set of 4-arylthiazolylhydrazones derived from 1-indanones (TZHs) previously synthesized and assayed against Trypanosoma cruzi, the causative agent of Chagas disease, were explored in terms of conformational analysis. We found that TZHs can adopt four minimum energy conformations: cis (A, B and C) and trans. The possible bioactive conformation was selected by a 3D-QSAR model. Different molecular parameters were calculated to produce QSAR second-generation models. These QSAR results are discussed in conjunction with conformational analysis from molecular modeling studies. The main factor to determine the activity of the compounds was the partial charge at the N(3) atom (qN3). The predictive ability of the QSAR equations proposed was experimentally validated. The QSAR models developed in this study will be helpful to design novel potent TZHs.
authors.affiliation: Química Medicinal, Departamento de Farmacología, IQUIMEFA (UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 1113 Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Guido J
authors.initials: GJ
authors.lastname: Noguera
authors.affiliation: Química Medicinal, Departamento de Farmacología, IQUIMEFA (UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 1113 Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Lucas E
authors.initials: LE
authors.lastname: Fabian
authors.affiliation: Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP, UBA-CONICET), Hospital de Clínicas José de San Martín, Avenida Córdoba 2351, 1120 Ciudad Autónoma de Buenos Aires, Argentina.
authors.forename: Elisa
authors.initials: E
authors.lastname: Lombardo
authors.affiliation: Química Medicinal, Departamento de Farmacología, IQUIMEFA (UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 1113 Ciudad Autónoma de Buenos Aires, Argentina. Electronic address: lfinkiel@ffyb.uba.ar.
authors.forename: Liliana
authors.initials: L
authors.lastname: Finkielsztein
mesh_terms: D000981:Antiprotozoal Agents / Q000737:chemistry* / Q000494:pharmacology; D006835:Hydrazones / Q000737:chemistry* / Q000494:pharmacology; D007189:Indans / Q000737:chemistry*; D008968:Molecular Conformation; D021281:Quantitative Structure-Activity Relationship; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000254:growth & development
chemical_list: D000981:Antiprotozoal Agents; D006835:Hydrazones; D007189:Indans
keywords: Anti-trypanosomal activity; Chagas disease; Conformational analysis; QSAR; Thiazolylhydrazones