Scheiffer Gustavo, Domingues Karime Zeraik Abdalla, Gorski Daniela, Cobre Alexandre de Fátima, Lazo Raul Edison Luna, Borba Helena Hiemisch Lobo, Ferreira Luana Mota, Pontarolo Roberto
Postgraduate Program in Pharmaceutical Sciences, Department of Pharmacy, Federal University of Paraná, Curitiba 80210-170, Paraná, Brazil.
EXCLI J. 2024 Sep 3;23:1117-1169. doi: 10.17179/excli2024-7552. eCollection 2024.
The shortage of treatment options for leishmaniasis, especially those easy to administer and viable for deployment in the world's poorest regions, highlights the importance of employing these strategies to cost-effectively investigate repurposing candidates. This scoping review aims to map the studies using methodologies for drug repurposing against leishmaniasis. This study followed JBI recommendations for scoping reviews. Articles were searched on PubMed, Scopus, and Web of Science databases using keywords related to leishmaniasis and methods for drug discovery, without publication date restrictions. The selection was based on primary studies involving computational methods for antileishmanial drug repurposing. Information about methodologies, obtained data, and outcomes were extracted. After the full-text appraisal, 34 studies were included in this review. Molecular docking was the preferred method for evaluating repurposing candidates (n=25). Studies reported 154 unique ligands and 72 different targets, sterol 14-alpha demethylase and trypanothione reductase being the most frequently reported. screening was able to correctly pinpoint some known active pharmaceutical classes and propose previously untested drugs. Fifteen drugs investigated exhibited low micromolar inhibition (IC < 10 µM) of spp. . In conclusion, several repurposing candidates are yet to be investigated and . Future research could expand the number of targets screened and employ advanced methods to optimize drug selection, offering new starting points for treatment development. See also the graphical abstract(Fig. 1).
利什曼病治疗方案的短缺,尤其是那些易于给药且可在世界最贫困地区推广应用的方案,凸显了采用这些策略以经济高效地研究重新利用药物候选物的重要性。本综述旨在梳理使用药物重新利用方法治疗利什曼病的研究。本研究遵循了循证卫生保健中心(JBI)关于综述的建议。在PubMed、Scopus和科学网数据库中使用与利什曼病及药物发现方法相关的关键词进行文献检索,无出版日期限制。选择基于涉及抗利什曼病药物重新利用计算方法的原始研究。提取了有关方法、获得的数据和结果的信息。经过全文评估,本综述纳入了34项研究。分子对接是评估重新利用候选物的首选方法(n = 25)。研究报告了154种独特的配体和72个不同的靶点,其中甾醇14-α-脱甲基酶和锥虫硫醇还原酶是最常报告的靶点。筛选能够正确确定一些已知的活性药物类别,并提出以前未测试过的药物。所研究的15种药物对利什曼原虫属表现出低微摩尔抑制作用(IC<10µM)。总之,仍有几种重新利用药物的候选物有待研究。未来的研究可以扩大筛选靶点的数量,并采用先进方法优化药物选择,为治疗开发提供新的起点。另见图1(图形摘要)。
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