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克服结核病治疗中的原核生物/真核生物障碍:抗寄生虫药物重新利用和使用的前景。

Overcoming the Prokaryote/Eukaryote Barrier in Tuberculosis Treatment: A Prospect for the Repurposing and Use of Antiparasitic Drugs.

作者信息

Ezquerra-Aznárez José Manuel, Almeida da Silva Pedro E, Aínsa José A

机构信息

Departamento de Microbiología, Facultad de Medicina, Instituto de Biocomputación y Física de Sistemas Complejos (BIFI), Universidad de Zaragoza, 50009 Zaragoza, Spain.

Programa de Pós-Graduação em Ciências da Saúde, Faculdade de Medicina, Universidade Federal do Rio Grande, Rio Grande 96200-190, Brazil.

出版信息

Microorganisms. 2021 Nov 11;9(11):2335. doi: 10.3390/microorganisms9112335.

Abstract

Antimicrobial resistance, the so-called , is pushing industry and academia to find novel antimicrobial agents with new mechanisms of action in order to be active against susceptible and drug-resistant microorganisms. In the case of tuberculosis, the need of novel anti-tuberculosis drugs is specially challenging because of the intricate biology of its causative agent, . The repurposing of medicines has arisen in recent years as a fast, low-cost, and efficient strategy to identify novel biomedical applications for already approved drugs. This review is focused on anti-parasitic drugs that have additionally demonstrated certain levels of anti-tuberculosis activity; along with this, natural products with a dual activity against parasites and against are discussed. A few clinical trials have tested antiparasitic drugs in tuberculosis patients, and have revealed effective dose and toxicity issues, which is consistent with the natural differences between tuberculosis and parasitic infections. However, through medicinal chemistry approaches, derivatives of drugs with anti-parasitic activity have become successful drugs for use in tuberculosis therapy. In summary, even when the repurposing of anti-parasitic drugs for tuberculosis treatment does not seem to be an easy job, it deserves attention as a potential contributor to fuel the anti-tuberculosis drug pipeline.

摘要

抗菌药物耐药性,即所谓的……,正促使业界和学术界寻找具有新作用机制的新型抗菌药物,以便对敏感和耐药微生物都具有活性。就结核病而言,由于其病原体……复杂的生物学特性,对新型抗结核药物的需求尤其具有挑战性。药物重新利用近年来已成为一种快速、低成本且高效的策略,用于为已批准的药物确定新的生物医学应用。本综述重点关注已额外显示出一定水平抗结核活性的抗寄生虫药物;与此同时,还讨论了对寄生虫和……具有双重活性的天然产物。一些临床试验已在结核病患者中测试了抗寄生虫药物,并揭示了有效剂量和毒性问题,这与结核病和寄生虫感染之间的天然差异一致。然而,通过药物化学方法,具有抗寄生虫活性的药物衍生物已成为用于结核病治疗的成功药物。总之,即使将抗寄生虫药物重新用于结核病治疗似乎并非易事,但作为为抗结核药物研发提供助力的潜在因素,它值得关注。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0372/8622410/6572fc81b00b/microorganisms-09-02335-g001.jpg

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