Mott Bryan T, Cheng Ken Chih-Chien, Guha Rajarshi, Kommer Valerie P, Williams David L, Vermeire Jon J, Cappello Michael, Maloney David J, Rai Ganesha, Jadhav Ajit, Simeonov Anton, Inglese James, Posner Gary H, Thomas Craig J
Department of Chemistry, Zanvyl Krieger School of Arts and Sciences, The Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland, 21218, USA ; Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, 20892, USA.
Medchemcomm. 2012 Dec;3(12):1505-1511. doi: 10.1039/C2MD20238G.
Parasitic diseases continue to have a devastating impact on human populations worldwide. Lack of effective treatments, the high cost of existing ones, and frequent emergence of resistance to these agents provide a strong argument for the development of novel therapies. Here we report the results of a hybrid approach designed to obtain a dual acting molecule that would demonstrate activity against a variety of parasitic targets. The antimalarial drug amodiaquine has been covalently joined with a nitric oxide-releasing furoxan to achieve multiple mechanisms of action. Using in vitro and ex vivo assays, the hybrid molecule shows activity against three parasites - Plasmodium falciparum, Schistosoma mansoni, and Ancylostoma ceylanicum.
寄生虫病继续对全球人类群体产生毁灭性影响。缺乏有效的治疗方法、现有治疗方法成本高昂以及对这些药物的耐药性频繁出现,都有力地支持了开发新型疗法的必要性。在此,我们报告一种混合方法的结果,该方法旨在获得一种具有双重作用的分子,该分子将对多种寄生虫靶点显示活性。抗疟药物阿莫地喹已与释放一氧化氮的呋咱共价连接,以实现多种作用机制。通过体外和离体试验,该杂交分子对三种寄生虫——恶性疟原虫、曼氏血吸虫和锡兰钩虫显示出活性。