López-Vallejo Fabian, Castillo Rafael, Yépez-Mulia Lilián, Medina-Franco José L
Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port St. Lucie, FL 34987, USA.
J Biomol Screen. 2011 Sep;16(8):862-8. doi: 10.1177/1087057111414902. Epub 2011 Aug 5.
Parasitic infections caused by Entamoeba histolytica are still major threats against public health, especially in developing countries. Although current therapies exist, the problems associated with parasite resistance and negative side effects make it imperative to search for new therapeutic agents. A systematic scaffold analysis reported herein of a public database containing 474 antiamoebic compounds reveals that benzimidazole is the most active scaffold reported thus far. To gain insights into the antiamoebic activity of novel compounds, the authors report herein the biological activity of 12 compounds, including benzotriazole and indazole derivatives, scaffolds not previously tested against E. histolytica. Compounds with the benzotriazole and indazole scaffolds showed low micromolar activity (IC(50) = 0.304 and 0.339 µM) and are more active than metronidazole, which is the drug of choice used for the treatment of amebiosis. The novel compounds have similar properties to approved drugs. Compounds with novel scaffolds represent promising starting points of an optimization program against E. histolytica.
由溶组织内阿米巴引起的寄生虫感染仍然是对公共卫生的主要威胁，尤其是在发展中国家。尽管目前存在治疗方法，但与寄生虫耐药性和负面副作用相关的问题使得寻找新的治疗药物势在必行。本文报道的对一个包含474种抗阿米巴化合物的公共数据库进行的系统支架分析表明，苯并咪唑是迄今为止报道的最具活性的支架。为了深入了解新型化合物的抗阿米巴活性，作者在此报告了12种化合物的生物活性，包括苯并三唑和吲唑衍生物，这些支架以前未针对溶组织内阿米巴进行过测试。具有苯并三唑和吲唑支架的化合物显示出低微摩尔活性（IC(50)=0.304和0.339μM），并且比甲硝唑更具活性，甲硝唑是用于治疗阿米巴病的首选药物。这些新型化合物具有与已批准药物相似的性质。具有新型支架的化合物代表了针对溶组织内阿米巴的优化计划的有希望的起点。
