Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, México, CDMX 04510, Mexico.
Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, IMSS, México, CDMX 06720, Mexico.
Eur J Med Chem. 2017 Sep 8;137:211-220. doi: 10.1016/j.ejmech.2017.05.058. Epub 2017 May 29.
A series of twelve new 2-(methylthio)-1H-benzimidazole-5-carboxamide derivatives (1-12) were synthesized and their antiparasitic activity was tested in vitro against Giardia intestinalis, Trichomonas vaginalis and Entamoeba histolytica. Experimental evaluations showed IC values within the nanomolar range for all tested compounds, some showing higher activity than metronidazole and albendazole. A chemoinformatic study was used to compare the structure-activity relationship of the synthesized carboxamides with those of 91 previously studied benzimidazoles, and with some Nitazoxanide-N-methylbenzimidazole hybrids recently synthetized by our group. Compounds 1 and 3 were identified as prominent selective compounds against T. vaginalis and G. intestinalis, respectively, while compound 4 was found to be of broad spectrum against the three protozoans.
合成了一系列十二种新的 2-(甲硫基)-1H-苯并咪唑-5-甲酰胺衍生物（1-12），并在体外对肠道贾第鞭毛虫、阴道毛滴虫和溶组织内阿米巴进行了抗寄生虫活性测试。实验评估表明，所有测试化合物的 IC 值均在纳摩尔范围内，其中一些化合物的活性高于甲硝唑和阿苯达唑。化学信息学研究用于比较合成的羧酰胺与 91 种先前研究的苯并咪唑以及我们小组最近合成的一些硝唑尼特-N-甲基苯并咪唑杂化物的结构-活性关系。化合物 1 和 3 分别被鉴定为针对阴道毛滴虫和肠道贾第鞭毛虫的突出选择性化合物，而化合物 4 被发现对三种原生动物具有广谱活性。
