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Recent research progress on small molecule compounds and its derivatives of antiparasitic drugs
Chinese Chemical Letters ( IF 9.4 ) Pub Date : 2023-03-21 , DOI: 10.1016/j.cclet.2023.108359
Ting Wang , Lin Wang , Jun He , Li Chang , Jianyou Shi

Neglected tropical diseases (NTDs) refer to infectious diseases caused by multiple pathogens that are prevalent in hot, humid climates in tropical areas. With the global economic growth and the improvement of public health status, eliminating neglected tropical diseases will be of great significance to the healthy development of human beings. However, the number of drugs and vaccines for NTDs treatment is extremely limited, so it is urgent to develop new drugs. Since most NTDs are caused by parasites, this paper selected parasitic diseases with high morbidity and mortality, and focused on new effective therapeutic targets and excellent lead compounds for these diseases. Schistosomiasis, human African trypanosomiasis (HAT), Chagas disease, leishmaniasis, filariasis and toxoplasmosis correspond to a series targets such as smHDAC8, thioredoxin glutathione reductase (TGR), T. cruzi glucokinase (TcGlcK), phosphofructokinase (PFK), type IB topoisomerase, cell division cycle-2-related Kinase, sterolmethyl transferase, calumenin, dihydrofolate reductase (DHFR) and Toxoplasma gondii farnesyl-diphosphate synthase (TgFPPs). In this paper, the pharmacological effects of typical lead compounds corresponding to each disease, the structural characteristics of the mother nucleus and the pharmacological activities of the substituent. In addition, the binding patterns of some involved targets (such as smHDAC8) with corresponding lead compounds (such as compound 13) and the signaling pathways associated with gluconeogenesis, glycolysis, and pentose phosphate pathways are analyzed in detail. In this paper, the interaction mechanism between the lead compounds and the target were thoroughly discussed, in order to provide the research ideas of potential anti-parasite compounds, and further improve the understanding and prevention ability of such diseases of NTDs.



中文翻译:

抗寄生虫药物小分子化合物及其衍生物的研究进展

被忽视的热带病(NTD)是指由多种病原体引起的传染病,流行于热带地区炎热、潮湿的气候中。随着全球经济增长和公共卫生状况的改善,消除被忽视的热带病对人类的健康发展具有重要意义。然而,用于NTDs治疗的药物和疫苗数量极其有限,因此开发新药刻不容缓。由于大多数NTD是由寄生虫引起的,因此本文选择了发病率和死亡率较高的寄生虫病,重点寻找针对这些疾病的新的有效治疗靶点和优良的先导化合物。血吸虫病、人类非洲锥虫病(HAT)、南美锥虫病、利什曼病、丝虫病和弓形体病等对应一系列目标HDAC8、硫氧还蛋白谷胱甘肽还原酶 (TGR)、T. cruzi葡萄糖激酶 ( Tc GlcK)、磷酸果糖激酶 (PFK)、IB 型拓扑异构酶、细胞分裂周期 2 相关激酶、甾醇甲基转移酶、calumenin、二氢叶酸还原酶 (DHFR) 和弓形虫法基-二磷酸合酶( Tg FPP)。本文介绍了各疾病对应的典型先导化合物的药理作用、母核的结构特征以及取代基的药理活性。此外,一些涉及的靶点(例如sm HDAC8)与相应的先导化合物(例如化合物13)的结合模式)以及与糖异生、糖酵解和磷酸戊糖途径相关的信号传导途径进行了详细分析。本文对先导化合物与靶标之间的相互作用机制进行了深入探讨,以期提供潜在抗寄生虫化合物的研究思路,进一步提高对NTDs类疾病的认识和预防能力。

更新日期:2023-03-21
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