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利什曼病药物筛选方法的见解。

Insights into the drug screening approaches in leishmaniasis.

作者信息

Gopu Boobalan, Kour Parampreet, Pandian Ramajayan, Singh Kuljit

机构信息

Animal House Facility, Pharmacology Division, CSIR- Indian Institute of Integrative Medicine, Jammu 180001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.

Infectious Diseases Division, CSIR- Indian Institute of Integrative Medicine, Jammu 180001, India.

出版信息

Int Immunopharmacol. 2023 Jan;114:109591. doi: 10.1016/j.intimp.2022.109591. Epub 2022 Dec 20.

Abstract

Leishmaniasis, a tropically neglected disease, is responsible for the high mortality and morbidity ratio in poverty-stricken areas. Currently, no vaccine is available for the complete cure of the disease. Current chemotherapeutic regimens face the limitations of drug resistance and toxicity concerns indicating a great need to develop better chemotherapeutic leads that are orally administrable, potent, non-toxic, and cost-effective. The anti-leishmanial drug discovery process accelerated the desire for large-scale drug screening assays and high-throughput screening (HTS) technology to identify new chemo-types that can be used as potential drug molecules to control infection. Using the HTS approach, about one million compounds can be screened daily within the shortest possible time for biological activity using automation tools, miniaturized assay formats, and large-scale data analysis. Classical and modern in vitro screening assays have led to the progression of active compounds further to ex vivo and in vivo studies. In the present review, we emphasized on the HTS approaches employed in the leishmanial drug discovery program. Recent in vitro screening assays are widely explored to discover new chemical scaffolds. Developing appropriate experimental animal models and their related techniques is necessary to understand the pathophysiological processes and disease host responses, paving the way for unraveling novel therapies against leishmaniasis.

摘要

利什曼病是一种被忽视的热带疾病,在贫困地区导致了高死亡率和高发病率。目前,尚无疫苗可用于完全治愈该疾病。当前的化疗方案面临耐药性和毒性问题的限制,这表明迫切需要开发更好的化疗先导物,这些先导物应可口服、高效、无毒且具有成本效益。抗利什曼病药物的发现过程加速了对大规模药物筛选试验和高通量筛选(HTS)技术的需求,以识别可作为控制感染的潜在药物分子的新化学类型。使用HTS方法,利用自动化工具、小型化检测形式和大规模数据分析,每天可在最短时间内筛选约100万种化合物的生物活性。经典和现代的体外筛选试验已使活性化合物进一步进入离体和体内研究阶段。在本综述中,我们重点介绍了利什曼病药物发现计划中采用的HTS方法。最近广泛探索体外筛选试验以发现新的化学骨架。开发合适的实验动物模型及其相关技术对于理解病理生理过程和疾病宿主反应是必要的,为揭示抗利什曼病的新疗法铺平道路。

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