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抗癌药物用于治疗细菌感染的重新利用。

Repurposing of Anticancer Drugs for the Treatment of Bacterial Infections.

作者信息

Soo Valerie W C, Kwan Brian W, Quezada Héctor, Castillo-Juárez Israel, Pérez-Eretza Berenice, García-Contreras Silvia Julieta, Martínez-Vázquez Mariano, Wood Thomas K, García-Contreras Rodolfo

机构信息

Department of Chemical Engineering, Pennsylvania State University, Philadelphia, United States.

Laboratorio de Investigación en Inmunología y Proteómica, Hospital Infantil de México Federico Gómez, Mexico City, Mexico.

出版信息

Curr Top Med Chem. 2017;17(10):1157-1176. doi: 10.2174/1568026616666160930131737.

Abstract

Despite the fact that bacterial infections are one of the leading causes of death worldwide and that mortality rates are increasing at alarming rates, no new antibiotics have been produced by the pharmaceutical industry in more than a decade. The situation is so dire that the World Health Organization warned that we may enter a "post-antibiotic era" within this century; accordingly, bacteria resistant against all known antibiotics are becoming common and already producing untreatable infections. Although several novel approaches to combat bacterial infections have been proposed, they have yet to be implemented in clinical practice. Hence, we propose that a more plausible and faster approach is the utilization of drugs originally developed for other purposes besides antimicrobial activity. Among these are some anticancer molecules proven effective in vitro for eliminating recalcitrant, multidrug tolerant bacteria; some of which also protect animals from infections and recently are undergoing clinical trials. In this review, we highlight the similarities between cancer cells/tumors and bacterial infections, and present evidence that supports the utilization of some anticancer drugs, including 5-fluorouracil (5-FU), gallium (Ga) compounds, and mitomycin C, as antibacterials. Each of these drugs has some promising properties such as broad activity (all three compounds), dual antibiotic and antivirulence properties (5-FU), efficacy against multidrug resistant strains (Ga), and the ability to kill metabolically dormant persister cells which cause chronic infections (mitomycin C).

摘要

尽管细菌感染是全球主要死因之一,且死亡率正以惊人的速度上升,但制药行业已有十多年未生产出新的抗生素。形势极为严峻,世界卫生组织警告称,我们可能在本世纪内进入“后抗生素时代”;相应地,对所有已知抗生素具有抗性的细菌正变得普遍,且已导致无法治疗的感染。尽管已经提出了几种对抗细菌感染的新方法,但它们尚未在临床实践中得到应用。因此,我们提出一种更可行、更快的方法是利用最初为抗菌活性以外的其他目的开发的药物。其中包括一些在体外已被证明对消除顽固的、耐多药细菌有效的抗癌分子;其中一些还能保护动物免受感染,并且最近正在进行临床试验。在这篇综述中,我们强调癌细胞/肿瘤与细菌感染之间的相似性,并提供证据支持使用一些抗癌药物作为抗菌剂,包括5-氟尿嘧啶(5-FU)、镓(Ga)化合物和丝裂霉素C。这些药物中的每一种都具有一些有前景的特性,如广泛的活性(所有三种化合物)、双重抗生素和抗毒力特性(5-FU)、对耐多药菌株的疗效(Ga)以及杀死导致慢性感染的代谢休眠持留菌的能力(丝裂霉素C)。

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