Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Eur J Med Chem. 2018 May 10;151:248-260. doi: 10.1016/j.ejmech.2018.03.083. Epub 2018 Mar 31.
In the search for new antifungal agents, a novel series of fifteen hydrazine-thiazole derivatives was synthesized and assayed in vitro against six clinically important Candida and Cryptococcus species and Paracoccidioides brasiliensis. Eight compounds showed promising antifungal activity with minimum inhibitory concentration (MIC) values ranging from 0.45 to 31.2 μM, some of them being equally or more active than the drug fluconazole and amphotericin B. Active compounds were additionally tested for toxicity against human embryonic kidney (HEK-293) cells and none of them exhibited significant cytotoxicity, indicating high selectivity. Molecular modeling studies results corroborated experimental SAR results, suggesting their use in the design of new antifungal agents.
在寻找新的抗真菌药物的过程中，我们合成了一系列十五个新的肼噻唑衍生物，并在体外对六种重要的临床念珠菌和隐球菌物种以及巴西副球孢子菌进行了检测。八种化合物表现出有希望的抗真菌活性，最低抑菌浓度（MIC）值范围为 0.45 至 31.2 μM，其中一些与药物氟康唑和两性霉素 B 相当或更具活性。活性化合物还针对人胚肾（HEK-293）细胞进行了毒性测试，它们均没有表现出明显的细胞毒性，表明它们具有很高的选择性。分子建模研究结果证实了实验 SAR 结果，这表明它们可用于设计新的抗真菌药物。
