Torres-Gómez Héctor, Hernández-Núñez Emanuel, León-Rivera Ismael, Guerrero-Alvarez Jorge, Cedillo-Rivera Roberto, Moo-Puc Rosa, Argotte-Ramos Rocío, Rodríguez-Gutiérrez María Del Carmen, Chan-Bacab Manuel Jesús, Navarrete-Vázquez Gabriel
Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos 62209, Mexico.
Bioorg Med Chem Lett. 2008 Jun 1;18(11):3147-51. doi: 10.1016/j.bmcl.2008.05.009. Epub 2008 May 4.
A series of ten novel hybrids from benzimidazole and pentamidine were prepared using a short synthetic route. Each compound was tested in vitro against the protozoa Trichomonas vaginalis, Giardia lamblia, Entamoeba histolytica, Leishmania mexicana, and Plasmodium berghei, in comparison with pentamidine and metronidazole. Some analogues showed high bioactivity in the low micromolar range (IC(50)<1 microM) against the first four protozoa, which make them significantly more potent than either standard. 1,5-bis[4-(5-methoxy-1H-benzimidazole-2-yl)phenoxy]pentane (2) was 3- and 9-fold more potent againstG. lamblia than metronidazole and pentamidine, respectively. This compound was 23-, 108-, and 13-fold more active than pentamidine against T. vaginalis, E. histolytica and L. mexicana, respectively. Studying further structure-activity relationships through the use of bioisosteric substitution in these hybrids should provide new leads against protozoal diseases.
通过一条简短的合成路线制备了一系列由苯并咪唑和喷他脒组成的十种新型杂合物。与喷他脒和甲硝唑相比，对每种化合物进行了针对原生动物阴道毛滴虫、蓝氏贾第鞭毛虫、溶组织内阿米巴、墨西哥利什曼原虫和伯氏疟原虫的体外测试。一些类似物对前四种原生动物在低微摩尔范围内（IC(50)<1 microM）表现出高生物活性，这使得它们比两种标准药物的效力都显著更高。1,5-双[4-(5-甲氧基-1H-苯并咪唑-2-基)苯氧基]戊烷（2）对蓝氏贾第鞭毛虫的效力分别比甲硝唑和喷他脒高3倍和9倍。该化合物对阴道毛滴虫、溶组织内阿米巴和墨西哥利什曼原虫的活性分别比喷他脒高23倍、108倍和13倍。通过在这些杂合物中使用生物电子等排体取代来进一步研究构效关系，应该能为抗原生动物疾病提供新的线索。
