Leite Ana Cristina Lima, Moreira Diogo Rodrigo de M, Cardoso Marcos V de O, Hernandes Marcelo Zaldini, Alves Pereira Valéria R, Silva Ricardo O, Kiperstok Alice C, Lima Milena da S, Soares Milena B P
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.
ChemMedChem. 2007 Sep;2(9):1339-45. doi: 10.1002/cmdc.200700022.
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).
近年来的研究表明,克氏锥虫半胱氨酸蛋白酶克氏锥虫蛋白酶(TCC)是一个有效的化疗靶点。在此,我们描述了一个芳基-4-氧代噻唑基腙的小型文库,该文库已在针对克氏锥虫细胞培养物的试验中进行了测试。所进行的对接研究表明,这些化合物是TCC酶的潜在配体。该系列中最有前景的化合物,N-(4-氧代-5-乙基-2'-噻唑啉-2-基)-N'-苯基硫代-(Z)-亚乙基腙(6 f),在与哺乳动物细胞的体外试验中,在非细胞毒性浓度下表现出非常高的活性,并且其效力与硝呋替莫(Nfx)和苯并硝唑(Bdz)等参考药物相当。