Química Medicinal, Departamento de Farmacología, Facultad de Farmacia y Bioquímica., Universidad de Buenos Aires, Junín 956, 1113, Ciudad Autónoma de Buenos Aires, Argentina.
Eur J Med Chem. 2012 Sep;55:155-63. doi: 10.1016/j.ejmech.2012.07.013. Epub 2012 Jul 20.
A series of novel 4-arylthiazolylhydrazones (TZHs) derived from 1-indanones were synthesized in good yields (66-92%) in a simple procedure using microwave irradiation and then characterized by spectroscopy studies. The compounds were evaluated for their in vitro anti-Trypanosoma cruzi activity against the epimastigote, trypomastigote and amastigote forms of the parasite. Most TZHs displayed excellent activity, and were more potent and selective than the reference drug Benznidazole, used in the current chemotherapy. Analysis of the free sterols from parasite incubated with the compounds showed that inhibition of ergosterol biosynthesis is a possible target for the action of these new TZHs. In particular, TZH 9 emerged as a promising antichagasic compound to be evaluated in animal models.
一系列新型的 4-芳基噻唑基腙（TZHs）是由 1-茚酮合成的，产率高（66-92%），采用微波辐射的简单方法，然后通过光谱研究进行了表征。对化合物进行了体外抗 Trypanosoma cruzi 活性评价，针对寄生虫的epimastigote、trypomastigote 和 amastigote 形式。大多数 TZHs 表现出优异的活性，比目前化疗中使用的参考药物 Benznidazole 更有效、更具选择性。对与化合物孵育的寄生虫中的游离甾醇进行分析表明，抑制麦角甾醇生物合成可能是这些新 TZHs 作用的靶点。特别是 TZH 9 作为一种有前途的抗恰加斯病化合物，将在动物模型中进行评估。
