PostGraduation Program in Technological Development and Innovation in Medicines, Federal University of Paraíba, João Pessoa CEP 58051-970, Brazil.
PECET-Facultad de Medicina, Universidad de Antioquia, Medellín Calle 70 # 52-21, Colombia.
Molecules. 2020 Jul 11;25(14):3178. doi: 10.3390/molecules25143178.
In low-income populations, neglected diseases are the principal cause of mortality. Of these, leishmaniasis and malaria, being parasitic, protozoan infections, affect millions of people worldwide and are creating a public health problem. The present work evaluates the leishmanicidal and antiplasmodial action of a series of twelve -coumaric acid derivatives. Of the tested derivatives, eight presented antiparasitic activities -, -. The hexyl -coumarate derivative () (4.14 ± 0.55 μg/mL; selectivity index (SI) = 2.72) showed the highest leishmanicidal potency against the amastigote form. The results of the molecular docking study suggest that this compound inhibits aldehyde dehydrogenase (ALDH), mitogen-activated kinase protein (MPK4), and DNA topoisomerase 2 (TOP2), all of which are key enzymes in the development of . The data indicate that these enzymes interact via Van der Waals bonds, hydrophobic interactions, and hydrogen bonds with phenolic and aliphatic parts of this same compound. Of the other compounds analyzed, methyl -coumarate (64.59 ± 2.89 μg/mL; IS = 0.1) demonstrated bioactivity against . The study reveals that esters presenting a -coumarate substructure are promising for use in synthesis of derivatives with good antiparasitic profiles.
在低收入人群中，被忽视的疾病是主要的死亡原因。其中，寄生虫病利什曼病和疟疾，作为原生动物感染，影响着全世界数百万人，并正在造成公共卫生问题。本工作评估了一系列十二 - 香豆酸衍生物的杀利什曼原虫和抗疟原虫作用。在所测试的衍生物中，有八种具有驱虫活性 - 。己基 - 香豆酸酯衍生物 ()（4.14 ± 0.55 μg/mL；选择性指数（SI）= 2.72）对前鞭毛体形式表现出最高的杀利什曼原虫活性。分子对接研究的结果表明，该化合物抑制醛脱氢酶（ALDH）、丝裂原活化蛋白激酶蛋白（MPK4）和 DNA 拓扑异构酶 2（TOP2），这些都是的关键酶。数据表明，这些酶通过范德华键、疏水相互作用和氢键与该化合物的酚和脂肪部分相互作用。在所分析的其他化合物中，香豆酸甲酯（64.59 ± 2.89 μg/mL；IS = 0.1）对表现出生物活性。该研究表明，具有 - 香豆酸结构的酯类具有良好的驱虫特性，有望用于合成衍生物。
