title: Synthesis, Cruzain docking, and in vitro studies of aryl-4-oxothiazolylhydrazones against Trypanosoma cruzi.
abstract: Research in recent years has demonstrated that the Trypanosoma cruzi cysteine protease cruzain (TCC) is a valid chemotherapeutic target. Herein we describe a small library of aryl-4-oxothiazolylhydrazones that have been tested in assays against T. cruzi cell cultures. The docking studies carried out suggest that these compounds are potential ligands for the TCC enzyme. The most promising compound of this series, N-(4-oxo-5-ethyl-2'-thiazolin-2-yl)-N'-phenylthio-(Z)-ethylidenehydrazone (6 f), was shown to be very active at non-cytotoxic concentrations in in vitro assays with mammalian cells and has a potency comparable with reference drugs such as nifurtimox (Nfx) and benznidazole (Bdz).
authors.affiliation: Laboratório de Planejamento, Avaliação e Síntese de Fármacos-LABSINFA, Departamento de Ciências Farmacêuticas, Universidade Federal de Pernambuco, Rua Prof. Artur Sá S/N, Cidade Universitária, 50740-520, Recife, PE, Brazil. ana.leite@pq.cnpq.br
authors.forename: Ana Cristina Lima
authors.initials: AC
authors.lastname: Leite
authors.forename: Diogo Rodrigo de M
authors.initials: DR
authors.lastname: Moreira
authors.forename: Marcos V de O
authors.initials: MV
authors.lastname: Cardoso
authors.forename: Marcelo Zaldini
authors.initials: MZ
authors.lastname: Hernandes
authors.forename: Valéria R
authors.initials: VR
authors.lastname: Alves Pereira
authors.forename: Ricardo O
authors.initials: RO
authors.lastname: Silva
authors.forename: Alice C
authors.initials: AC
authors.lastname: Kiperstok
authors.forename: Milena da S
authors.initials: Mda S
authors.lastname: Lima
authors.forename: Milena B P
authors.initials: MB
authors.lastname: Soares
mesh_terms: D000818:Animals; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D006835:Hydrazones / Q000138:chemical synthesis* / Q000494:pharmacology*; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015800:Protozoan Proteins / Q000378:metabolism*; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D006835:Hydrazones; D015800:Protozoan Proteins; D014344:Trypanocidal Agents; D003546:Cysteine Endopeptidases; C074032:cruzain, Trypanosoma cruzi