Rolón Miriam, Peixoto de Abreu Lima Alejandro, Coronel Cathia, Vega Maria Celeste, Pandolfi Enrique, Rojas de Arias Antonieta
Centro para el Desarrollo de la Investigación Científica (CEDIC) (Diaz Gil Medicina laboratorial/FMB), Asunción, Paraguay.
Departamento de Química Orgánica, Facultad de Química, Universidad de la República, Montevideo, Uruguay.
J Infect Dev Ctries. 2019 Jun 30;13(6):565-576. doi: 10.3855/jidc.10622.
Chagas disease and Leishmaniasis are among the most important parasitic diseases. They are considered to be within the most relevant group of neglected tropical diseases and have been included as priorities for searching new drugs due to their several treatment limitations. These parasitic diseases caused by flagellated protozoans affect more than 20 million people predominantly in developing countries.
In this study, we prepared a series of 2-substituted 1,4-benzenediols by an efficient, green, and lithium salt-free synthesis in water/ethanol as solvent to test their anti-parasitic activity. All 36 phenolic derivatives were evaluated in vitro for their activity against T. cruzi epimastigotes, L. infantum, and L. braziliensis promastigotes, as well as their cytotoxicity on macrophage and fibroblast cell lines.
Based on the results obtained, the compounds that presented a methyl, trifluoromethyl or bromo group at the para-position of the second benzene ring were found the most active analogs, with higher selective index values on the three parasites assayed.
This evidence suggests that the anti-parasitic activity observed in these analogs is affected by the size of the group at the 4-position of the second ring, but not related with electronic factors.This study identified hit compounds with the potential to target several kinetoplastid parasites.
恰加斯病和利什曼病是最重要的寄生虫病之一。它们被认为是最相关的被忽视热带病群体之一，由于其多种治疗局限性，已被列为寻找新药的优先事项。这些由鞭毛虫原生动物引起的寄生虫病主要影响发展中国家的2000多万人。
在本研究中，我们在水/乙醇作为溶剂的条件下，通过高效、绿色且无锂盐的合成方法制备了一系列2-取代的1,4-苯二醇，以测试它们的抗寄生虫活性。对所有36种酚类衍生物进行了体外评估，以检测它们对克氏锥虫前鞭毛体、婴儿利什曼原虫和巴西利什曼原虫前鞭毛体的活性，以及它们对巨噬细胞和成纤维细胞系的细胞毒性。
根据所得结果，发现第二个苯环对位带有甲基、三氟甲基或溴基团的化合物是最具活性的类似物，在测定的三种寄生虫上具有更高的选择性指数值。
这一证据表明，在这些类似物中观察到的抗寄生虫活性受第二个环4位基团大小的影响，但与电子因素无关。本研究确定了具有靶向几种动基体寄生虫潜力的活性化合物。
