Hernández-Núñez Emanuel, Tlahuext Hugo, Moo-Puc Rosa, Moreno Diego, González-Díaz María Ortencia, Vázquez Gabriel Navarrete
CONACYT, Departamento de Recursos del Mar, Centro de Investigación y de Estudios Avanzados del IPN, Unidad Mérida, Mérida 97310, Yucatán, Mexico.
Centro de Investigaciones Químicas, Universidad Autónoma del Estado de Morelos, Cuernavaca 62210, Morelos, Mexico.
Molecules. 2017 Apr 4;22(4):579. doi: 10.3390/molecules22040579.
Parasitic diseases are a public health problem affecting millions of people worldwide. One of the scaffolds used in several drugs for the treatment of parasitic diseases is the benzimidazole moiety, a heterocyclic aromatic compound. This compound is a crucial pharmacophore group and is considered a privileged structure in medicinal chemistry. In this study, the benzimidazole core served as a model for the synthesis of a series of 2-(2-amino-5(6)-nitro-1-benzimidazol-1-yl)--arylacetamides - as benznidazole analogues. The in silico pharmacological results calculated with PASS platform exhibited chemical structures highly similar to known antiprotozoal drugs. Compounds 1-8 when evaluated in silico for acute toxicity by oral dosing, were less toxic than benznidazole. The synthesis of compounds - were carried out through reaction of 5(6)-nitro-1-benzimidazol-2-amine () with 2-chlroactemides -, in the presence of K₂CO₃ and acetonitrile as solvent, showing an inseparable mixture of two regioisomers with the -NO₂ group in position 5 or 6 with chemical yields of 60 to 94%. The prediction of the NMR spectra of molecule coincided with the experimental chemical displacements of the regioisomers. Comparisons between the NMR prediction and the experimental data revealed that the regioisomer -1,6-NO₂ predominated in the reaction. The in vitro antiparasitic activity of these compounds on intestinal unicellular parasites ( and ) and a urogenital tract parasite () were tested. Compound showed an IC of 3.95 μM and was 7 time more active against than benznidazole. Compounds and showed 4 times more activity against compared with benznidazole.
寄生虫病是一个影响全球数百万人的公共卫生问题。用于治疗寄生虫病的几种药物中所使用的一种骨架是苯并咪唑部分，它是一种杂环芳香化合物。该化合物是一个关键的药效基团，在药物化学中被认为是一种优势结构。在本研究中，苯并咪唑核心作为合成一系列2-(2-氨基-5(6)-硝基-1-苯并咪唑-1-基)-芳基乙酰胺——作为苄硝唑类似物的模型。使用PASS平台计算的计算机药理学结果显示，其化学结构与已知的抗原虫药物高度相似。化合物1-8通过口服给药进行计算机急性毒性评估时，毒性低于苄硝唑。化合物的合成是通过5(6)-硝基-1-苯并咪唑-2-胺（）与2-氯乙酰胺-在碳酸钾存在下，以乙腈为溶剂进行反应，得到两种区域异构体的不可分离混合物，-NO₂基团位于5或6位，化学产率为60%至94%。分子的核磁共振谱预测与区域异构体的实验化学位移相符。核磁共振预测与实验数据的比较表明，区域异构体-1,6-NO₂在反应中占主导地位。测试了这些化合物对肠道单细胞寄生虫（和）以及泌尿生殖道寄生虫（）的体外抗寄生虫活性。化合物显示IC为3.95μM，对的活性比苄硝唑高7倍。化合物和对的活性比苄硝唑高4倍。
