摘要
背景:尽管结核病流行病学在全球范围内呈积极趋势,但耐药菌株的增长率正敦促将新的抗结核药物引入临床实践。从热销药品到上市药品的新化学实体的开发是一个极其耗时和资源消耗的过程,其结果是不确定的。重新利用临床上使用过的药物可以成为开发有效治疗结核病的新药物的廉价替代品。 目的:了解临床应用抗结核药物的新作用机制。确定不同药效学组的药物作为治疗结核病的有效药物。在临床实践或临床试验中,应注意阐明再利用药物与新抗结核药物之间的关系。 方法:检索科学数据库中的关键词。 结果:回顾了一线和二线抗结核药物临床应用的最新情况和新的作用机制。此外,我们还发现,来自不同药效学组的大量临床使用药物有潜力用于治疗结核病,包括通常不用于治疗结核病的抗菌药物、他汀类药物、中枢神经系统药物(三环吩噻嗪类、抗抑郁药、抗惊厥药)、非甾体类抗炎药。常用药物、激酶抑制剂和其他(二甲双胍、二硫醚、维拉帕米、兰索拉唑)。再利用药物可能成为有效的抗结核药物,通过直接作用于分枝杆菌或作为辅助的宿主导向疗法发挥作用。 结论:在本综述中,适当研究老药是开发新型抗结核药物的有效手段。
关键词: 抗结核,作用机制,结核病,再利用药物,重新定位药物,滥交药物,多靶点药物。
Current Medicinal Chemistry
Title:Old Drugs and New Targets as an Outlook for the Treatment of Tuberculosis
Volume: 25 Issue: 38
关键词: 抗结核,作用机制,结核病,再利用药物,重新定位药物,滥交药物,多靶点药物。
摘要: Background: Despite of the globally positive trends in the epidemiology of tuberculosis, the increasing rates of drug-resistant strains are urging to introduce new antituberculars into clinical practice. Development of a new chemical entity from hit to marketed drug is an extremely time and resources consuming process with uncertain outcome. Repurposing of clinically used drugs can be a cheaper alternative to develop new drugs effective in the treatment of tuberculosis.
Objective: To extract the latest information on new mechanisms of action described or proposed for clinically used antitubercular drugs. To identify drugs from various pharmacodynamic groups as candidates for repurposing to become effective in combatting tuberculosis. Attention will be paid to elucidate the connection between repurposed drugs and new antituberculars in clinical practice or in clinical trials.
Methods: Scientific databases were searched for the keywords.
Results: We reviewed the latest aspects of usage and new mechanisms of action for both first-line and second-line antitubercular drugs in clinical practice. Further, we found that surprisingly large number of clinically used drugs from various pharmacodynamic groups have potential to be used in the treatment of tuberculosis, including antimicrobial drugs not typically used against tuberculosis, statins, CNS drugs (tricyclic phenothiazines, antidepressants, anticonvulsants), non-steroidal anti-inflammatory drugs, kinase inhibitors, and others (metformin, disulfiram, verapamil, lansoprazole). Repurposed drugs may become effective antituberculars, acting either by direct effects on mycobacteria or as adjunct, host-directed therapy.
Conclusion: In this review, we showed that proper research of old drugs is a very efficient tool to develop new antituberculars.
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Cite this article as:
Old Drugs and New Targets as an Outlook for the Treatment of Tuberculosis, Current Medicinal Chemistry 2018; 25 (38) . https://dx.doi.org/10.2174/0929867324666170920154325
DOI https://dx.doi.org/10.2174/0929867324666170920154325 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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