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克服抗生素耐药性:药物重新利用的潜力与陷阱

Overcoming antibiotic resistance: the potential and pitfalls of drug repurposing.

作者信息

Abavisani Mohammad, Khoshrou Alireza, Eshaghian Souzan, Karav Sercan, Sahebkar Amirhossein

机构信息

Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran.

Department of Molecular Biology and Genetics, Canakkale Onsekiz Mart University, Canakkale, Turkey.

出版信息

J Drug Target. 2025 Mar;33(3):341-367. doi: 10.1080/1061186X.2024.2424895. Epub 2024 Nov 12.

Abstract

Since its emergence shortly after the discovery of penicillin, antibiotic resistance has escalated dramatically, posing a significant health threat and economic burden. Drug repositioning, or drug repurposing, involves identifying new therapeutic applications for existing drugs, utilising their established safety profiles and pharmacological data to swiftly provide effective treatments against resistant pathogens. Several drugs, including otilonium bromide, penfluridol, eltrombopag, ibuprofen, and ceritinib, have demonstrated potent antibacterial activity against multidrug-resistant (MDR) bacteria. These drugs can disrupt biofilms, damage bacterial membranes, and inhibit bacterial growth. The combination of repurposed drugs with conventional antibiotics can reduce the required dosage of individual drugs, mitigate side effects, and delay the development of resistance, making it a promising strategy against MDR bacteria such as , , , and . Despite its promise, drug repurposing faces challenges such as potential off-target effects, toxicity, and regulatory and intellectual property issues, necessitating rigorous evaluations and strategic solutions. This article aims to explore the potential of drug repurposing as a strategy to combat antibiotic resistance, examining its benefits, challenges, and future prospects. We address the legal, economic, and practical challenges associated with repurposing existing drugs, highlight successful examples, and propose solutions to enhance the efficacy and viability of this approach in combating MDR bacterial infections.

摘要

自青霉素发现后不久出现以来,抗生素耐药性急剧上升,构成了重大的健康威胁和经济负担。药物重新定位,即药物再利用,涉及为现有药物确定新的治疗用途,利用其已确立的安全性概况和药理学数据,迅速提供针对耐药病原体的有效治疗方法。包括奥替溴铵、五氟利多、艾曲泊帕、布洛芬和色瑞替尼在内的几种药物,已显示出对多重耐药(MDR)细菌具有强大的抗菌活性。这些药物可破坏生物膜、损伤细菌膜并抑制细菌生长。重新利用的药物与传统抗生素联合使用可减少单个药物的所需剂量、减轻副作用并延缓耐药性的产生,使其成为对抗如 、 、 和 等多重耐药细菌的一种有前景的策略。尽管有前景,但药物重新定位面临着诸如潜在的脱靶效应、毒性以及监管和知识产权问题等挑战,这需要进行严格评估并制定战略解决方案。本文旨在探讨药物重新定位作为对抗抗生素耐药性策略的潜力,研究其益处、挑战和未来前景。我们阐述了与重新利用现有药物相关的法律、经济和实际挑战,突出成功案例,并提出提高该方法在对抗多重耐药细菌感染方面的疗效和可行性的解决方案。

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