期刊
CURRENT TOPICS IN MEDICINAL CHEMISTRY
卷 21, 期 21, 页码 1871-1899出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1568026621666210331152702
关键词
Chagas disease; Human African trypanosomiasis; Cruzain; Rhodesain; Drug discovery; Molecular modeling
资金
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior-Brazil (CAPES)
- National Council for Scientific and Technological Development (CNPq)
- Fundacao de Amaro a Pesquisa do Estado de Alagoas (FAPEAL)
This review discusses the development of cruzain and rhodesain inhibitors in the past 10 years, which could serve as a basis for the discovery of new trypanocidal drugs in the future.118 studies on inhibitors of cruzain and rhodesain were identified, indicating the potential for developing new treatments against Chagas disease and sleeping sickness.
Neglected tropical diseases (NTDs) are a group of approximately 20 diseases that affect part of the population in Sub-and Tropical countries. In the past, pharmaceutical industries and governmental agencies have invested in the control, elimination and eradication of such diseases. Among these diseases, Chagas disease (CD) and Human African trypanosomiasis (HAT) are a public health problem, mainly in the countries from the American continent and sub-Saharan African. In this context, the search for new therapeutic alternatives against such diseases has been growing in recent years, presenting cysteine proteases as the main strategy to discover new anti-trypanosomal drugs. Thus, cruzain and rhodesain enzymes are targets widely studied, since the cruzain is present in all stages of the parasite's life, related to the stages of proliferation and differentiation and infection of macrophages; while the rhodesain is related to the immune defense process. In addition, knowledge about the amino acid sequences and availability of X-ray complexes have stimulated the drug searching against these targets, mainly through molecular modeling studies. Thus, this review manuscript will be addressed to cruzain and rhodesain inhibitors developed in the last 10 years, which could provide basis for new lead compounds in the discovery of new trypanocidal drugs. We found 117 studies involving inhibitors of cruzain and rhodesain, being thiosemicarbazones, semicarbazones, N-acylhydrazones, thiazoles-hydrazone, thiazolidinones-hydrazones, oxadiazoles, triazoles, triazines, imidazoles, peptidomimetic, and others. All references were obtained using cruzain or rhodesain and inhibitor as keywords in Science Direct, Bentham Science, PubMed, Espacenet, Springer, ACS Publisher, Wiley, Taylor and Francis, and MDPI (Multidisciplinary Digital Publishing Institute) databases. Finally, we highlighted all these chemical classes of molecules to provide valuable information that could be used to design new inhibitors against Chagas disease and sleeping sickness in the future.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据