title: Design, synthesis and biological evaluation of new aryl thiosemicarbazone as antichagasic candidates.
abstract: The present work reports on the synthesis, biological assaying and docking studies of a series of 12 aryl thiosemicarbazones, which were planned to act over two main enzymes, cruzain and trypanothione reductase. These enzymes are used as targets of trypanocidal activity in Chagas disease control with a minimal mutagenic profile. Three p-nitroaromatic thiosemicarbazones showed high activity against Trypanosoma cruzi in in vitro assays (IC50 < 57 μM), and no mutagenic profile was observed in micronucleous tests. Although the in vitro inhibition test showed that 10-μM doses of eight compounds inhibited cruzain activity, no correlation was found between cruzain inhibition and trypanocidal activity.
authors.affiliation: Departamento de Fármacos e Medicamentos, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Rodovia Araraquara-Jaú Km 01, 14801-902 Araraquara, SP, Brazil. Electronic address: lorenablau@yahoo.com.br.
authors.forename: Lorena
authors.initials: L
authors.lastname: Blau
authors.forename: Renato Farina
authors.initials: RF
authors.lastname: Menegon
authors.forename: Gustavo H G
authors.initials: GH
authors.lastname: Trossini
authors.forename: João Vitor Dutra
authors.initials: JV
authors.lastname: Molino
authors.forename: Drielli Gomes
authors.initials: DG
authors.lastname: Vital
authors.forename: Regina Maria Barretto
authors.initials: RM
authors.lastname: Cicarelli
authors.forename: Gabriela Duó
authors.initials: GD
authors.lastname: Passerini
authors.forename: Priscila Longhin
authors.initials: PL
authors.lastname: Bosquesi
authors.forename: Chung Man
authors.initials: CM
authors.lastname: Chin
mesh_terms: D014355:Chagas Disease / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D013882:Thiosemicarbazones
keywords: Chagas disease; Cruzain; Docking; FJCDJOPKILSQQC-WUXMJOGZSA-N; IKXKPKRBUBTOBD-WUXMJOGZSA-N; JMULZUQMMLAALR-YRNVUSSQSA-N; JXVGNNBDZQLCNB-MXZHIVQLSA-N; MOLCDPMVIXILLZ-MXZHIVQLSA-N; Mutagenicity; NFJPLHYZNDOBTD-IZZDOVSWSA-N; OIHUOBSUZMQSOX-LFYBBSHMSA-N; Oxidative stress; QFZNMVFZOBJIQX-MHWRWJLKSA-N; ROSQBCLWTZWMGU-DHZHZOJOSA-N; Thiosemicarbazone; ULDWASCYNZEGGY-MXZHIVQLSA-N; VAOJXJAGBHUCPY-LFYBBSHMSA-N; VNXBTMDXSKKCLJ-XNTDXEJSSA-N