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

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, di-hydrofolate 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.& COPY; 2023 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Automated summary

This paper focuses on neglected tropical diseases caused by parasites and explores new therapeutic targets and lead compounds. It analyzes the interaction mechanisms between lead compounds and targets, as well as the signaling pathways associated with these diseases, in order to provide research ideas for potential anti-parasite compounds.