Adeyemi Oluyomi Stephen, Molina María Teresa, Eseola Abiodun Omokehinde, Fonseca-Berzal Cristina, Gómez-Barrio Alicia
Medicinal Biochemistry and Toxicology Laboratory, Department of Biological Sciences, PMB 1004, Landmark University, Omu-Aran. Nigeria.
Instituto de Química Médica (IQM-CSIC), Juan de la Cierva 3, 28006, Madrid. Spain.
Comb Chem High Throughput Screen. 2017;20(1):20-24. doi: 10.2174/1386207320666170110141907.
Current drugs available for the treatment of Chagas disease are fraught with several challenges including severe toxicity and limited efficacy. These factors coupled with the absence of effective drugs for treating the chronic stage of the disease have rendered the development of new drugs against Chagas disease a priority.
This study screened several imidazole-based compounds for anti-Trypanosoma potential.
Using an in vitro experimental infection model, several imidazole-based compounds were screened for anti-proliferative effect on Trypanosoma cruzi epimastigotes. Additionally, all test compounds were evaluated for unspecific cytotoxicity on L929 murine fibroblasts. Benznidazole (BZN) served as reference drug.
All test compounds demonstrated interesting trypanocidal potential with IC50 values in the μM range (1< 1C50 <8 μM). The activities of the test compounds compared favorably with BZN, which had an IC50 value ca. 30 μM. Conversely, most of the test compounds were highly cytotoxic, resulting in selectivity lower than that of BZN (SI > 9.42).
We provide evidence which implicate the imidazole-based compounds as potential prototypes for the development of anti-parasitic agents. Findings have far-reaching relevance to drug discovery efforts for trypanosomiasis.
目前可用于治疗恰加斯病的药物面临诸多挑战，包括严重的毒性和有限的疗效。这些因素，再加上缺乏治疗该疾病慢性阶段的有效药物，使得开发抗恰加斯病的新药成为当务之急。
本研究筛选了几种基于咪唑的化合物的抗锥虫潜力。
使用体外实验感染模型，筛选了几种基于咪唑的化合物对克氏锥虫前鞭毛体的抗增殖作用。此外，评估了所有测试化合物对L929小鼠成纤维细胞的非特异性细胞毒性。苯硝唑（BZN）作为参考药物。
所有测试化合物均显示出有趣的杀锥虫潜力，IC50值在微摩尔范围内（1 < IC50 < 8 μM）。测试化合物的活性与IC50值约为30 μM的BZN相比具有优势。相反，大多数测试化合物具有高度细胞毒性，导致选择性低于BZN（SI > 9.42）。
我们提供的证据表明，基于咪唑的化合物是开发抗寄生虫药物的潜在原型。这些发现对锥虫病的药物发现工作具有深远意义。
