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Recent research progress on small molecule compounds and its derivatives of antiparasitic drugs

Chinese Chemical Letters 2023年第10期34卷 35-47页

作者： Ting Wang Lin Wang Jun He Li Chang Jianyou Shi Department of Pharmacy Personalized Drug Therapy Key Laboratory of Sichuan ProvinceSichuan Academy of Medical Sciences&Sichuan Provincial People’s HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaChinese Academy of Sciences Sichuan Translational Medicine Research HospitalChengdu 610072China College of Food and Bioengineering Xihua UniversityChengdu 610039China Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China Emergency Intensive Care Unit Sichuan Academy of Medical Science&Sichuan Provincial People’s HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaChinese Academy of Sciences Sichuan Translational Medicine Research HospitalChengdu 610072China

Neglected tropical diseases(NTDs)refer to infectious diseases caused by multiple pathogens that are prevalent in hot,humid climates in tropical *** 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 ***,the number of drugs and vaccines for NTDs treatment is extremely limited,so it is urgent to develop new *** 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 ***,human African trypanosomiasis(HAT),Chagas disease,leishmaniasis,filariasis and toxoplasmosis correspond to a series targets such as smHDAC8,thioredoxin glutathione reductase(TGR),*** 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 *** 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 *** 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.

关键词： Neglected tropical disease parasite anti-parasite Mechanism Crystal structure

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