Eweas Ahmad F, Allam Gamal
Department of Medicinal Chemistry, Pharmaceutical and Drug Industries Division, National Research Centre, Giza, Egypt.
Department of Microbiology, College of Medicine, Taif University, Taif, Saudi Arabia; Immunology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt.
Mol Biochem Parasitol. 2018 Oct;225:94-102. doi: 10.1016/j.molbiopara.2018.09.004. Epub 2018 Oct 4.
Schistosomiasis represents a world health major problem affecting more than 206 million people worldwide. Up to date, praziquantel (PZQ) is the sole chemotherapeutic agent used in clinics for the treatment of schistosomiasis. The resistance to PZQ chemotherapy that has been emerged against some schistosome phenotypes represents the most serious PZQ-related problem so far. Therefore, it is clear that there is a substantial need to develop novel and effective antischistosomal agents in order to ensure the effective drug control of schistosomiasis in the future. It is well-documented that the thiol redox homeostasis of schistosomes is entirely based on a single enzyme named thioredoxin-glutathione reductase (TGR). Thus, TGR is an essential protein for the survival of schistosomes which means that TGR is a valid and promising target for the recent antischistosomal drug-discovery approaches. This review aimed to shed light on potential lead compounds that may inhibit TGR activity and consequently could be tested as a potential antischistsomal drugs. In the current review we discussed multiple drug discovery approaches for new compounds targeting TGR and its implementation.
血吸虫病是一个影响全球超过2.06亿人的重大世界卫生问题。迄今为止,吡喹酮(PZQ)是临床上用于治疗血吸虫病的唯一化疗药物。针对某些血吸虫表型出现的对PZQ化疗的抗性是迄今为止与PZQ相关的最严重问题。因此,显然迫切需要开发新型有效的抗血吸虫药物,以确保未来对血吸虫病进行有效的药物控制。有充分文献记载,血吸虫的硫醇氧化还原稳态完全基于一种名为硫氧还蛋白-谷胱甘肽还原酶(TGR)的单一酶。因此,TGR是血吸虫生存所必需的蛋白质,这意味着TGR是近期抗血吸虫药物发现方法的一个有效且有前景的靶点。本综述旨在阐明可能抑制TGR活性并因此可作为潜在抗血吸虫药物进行测试的潜在先导化合物。在当前综述中,我们讨论了针对TGR的新化合物的多种药物发现方法及其实施情况。