抗利什曼原虫药物开发：现代分子化学工具和研究策略综述

Title:Antileishmanial Drug Development: A Review of Modern Molecular Chemical Tools and Research Strategies

Volume: 28 Issue: 31

关键词: 利什曼病、表型筛选、基于目标的筛选、CRISP/Cas9、粘粒文库、蛋白酶体、N-肉豆蔻酰化、细胞周期蛋白依赖性激酶。

摘要: Leishmaniasis, a complex disease caused by at least 20 species of unicellular parasites of the genus Leishmania, disproportionately affects impoverished regions of about 90 tropical and sub-tropical countries. Currently available antileishmanial therapies, particularly for visceral leishmaniasis, are severely limited, with treatment outcome depending on many factors, including the immune status of the patient, comorbidities, malnutrition, and socio-economic conditions in the patient’s geographic location. There is an urgent need for new therapeutics, particularly new effective oral drugs, for visceral leishmaniasis. Despite the availability of the Leishmania genome sequence information and significant research into the biology of the parasites, antileishmanial drug development is hampered by the lack of knowledge about druggable targets in the parasite and difficulties in identifying the molecular targets of compounds that show activity. In this context, we analyzed recent progress in antileishmanial drug development programs, which take advantage of different powerful approaches, such as high-throughput screening of compound libraries, recent developments in genetic methods for assessing essentiality of parasite genes, and chemical, genetic, and proteomics-based target discovery and target validation methods.

Cite this article as:

Antileishmanial Drug Development: A Review of Modern Molecular Chemical Tools and Research Strategies, Current Medicinal Chemistry 2021; 28 (31) . https://dx.doi.org/10.2174/0929867328666201125121018