Abstract：
Synthetic drugs currently prescribed for the treatment of Human African Trypanosomiasis (HAT) are non-specific, toxic, demand extended therapeutic regimes and are of varying efficacy. Along with the challenging demographic and socio-economic hurdles, the everincreasing risk of drug resistance is another major problem to be addressed. Cysteine protease, Heat shock proteins (HSP-90), Trypanothione reductase (TR), Farnesyl diphosphate synthase, Glucose-6-phosphate dehydrogenase, UP-4-galactose epimerase, and Cytidine triphosphate synthetase are potential enzymatic targets for the development of novel inhibitors against HAT which are the main focus of this review. The potential enzymatic targets of Trypanosoma brucei, especially small molecules like cysteine proteases and heat shock proteins are identified as major candidates for the sustenance of the parasite, their proliferation, infection, and spread of the disease. The development of new compounds to combat the disease by thorough ligand modification has been explored in the current review. Extracting these compounds and studying their efficacy, toxicity, and target mechanism extensively, this review has proposed a list of different compounds, including some synthetic and natural compounds along with multi-target inhibitors such as acoziborole, fexinidazole, etc. Potential inhibitors against these enzymatic targets of the T. brucei are important candidates for designing novel therapeutics against HAT. Multi-target inhibitors have also been identified as crucial molecules because of their potential advantage against the development of drug resistance.
摘要：
目前用于治疗人类非洲锥虫病（HAT）的合成药物是非特异性的，有毒,需要延长治疗方案，疗效各不相同。除了具有挑战性的人口和社会经济障碍，不断增加的耐药风险是另一个需要解决的主要问题。半胱氨酸蛋白酶,热休克蛋白（HSP-90），锥硫酮还原酶（TR），法尼基二磷酸合成酶，葡萄糖-6-磷酸脱氢酶,UP-4-半乳糖差向异构酶，三磷酸胞苷合成酶和三磷酸胞苷合成酶是开发抗HAT的新型抑制剂的潜在酶靶标，是本文综述的主要重点。布鲁氏锥虫的潜在酶学靶标，特别是小分子，如半胱氨酸蛋白酶和热休克蛋白被确定为主要的候选寄生物，他们的扩散，感染,和疾病的传播。在当前的综述中已经探索了通过彻底的配体修饰来对抗疾病的新化合物的开发。提取这些化合物并研究其功效，毒性,广泛的目标机制，这篇综述提出了不同化合物的清单，包括一些合成和天然化合物以及多靶点抑制剂，如acoziborole，非西硝唑,等。针对布鲁氏菌的这些酶靶标的潜在抑制剂是设计针对HAT的新疗法的重要候选物。多靶标抑制剂也已被鉴定为关键分子,因为它们具有对抗耐药性发展的潜在优势。
