Toward Combating Pseudomonas aeruginosa Infection, the Creation of Azithromycin Derivatives Based on a Trojan Horse Strategy

IF 3.5 4区医学 Q2 CHEMISTRY, MEDICINAL

ChemMedChem Pub Date : 2026-09-25 DOI:10.1002/cmdc.70498

Aoi Kimishima, Rina Suzuki, Taichi Kamo, Paul Wasuwanich, Hidehito Matsui, Sota Negami, Sota Honma, Yukiko Ujie, Naozumi Kondo, Hideaki Hanaki, Yukihiro Asami

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引用次数: 0

Abstract

Due to Pseudomonas aeruginosa (P. aeruginosa)’s inherent resistance to many antibiotics and the increasing incidence of multidrug-resistant (MDR) organisms, P. aeruginosa infection has become a growing global threat to humanity. Azithromycin (AZM) does not have prominent antibacterial activity against P. aeruginosa at a clinically reasonable level because of the bacteria’s outer membrane and efflux pump system; however, it does demonstrate other properties, including reduction of inflammation and suppression of P. aeruginosa virulence. With the promising potential of AZM as an anti-P. aeruginosa active compound, we proposed the application of a Trojan horse strategy to the synthesis of AZM derivatives. In this study, we designed and synthesized catechol-conjugated AZM derivatives and evaluated their anti-P. aeruginosa activity. One of the derivatives showed superior antibacterial activity to AZM, even against MDR P. aeruginosa clinical isolates.

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针对铜绿假单胞菌感染，基于特洛伊木马策略的阿奇霉素衍生物的创建。

由于铜绿假单胞菌（P. aeruginosa， P. aeruginosa）对多种抗生素的固有耐药性以及耐多药（MDR）生物的发病率不断上升，铜绿假单胞菌感染已成为对人类日益严重的全球性威胁。由于细菌的外膜和外排泵系统，阿奇霉素对铜绿假单胞菌的抑菌活性在临床合理水平上不明显；然而，它确实显示出其他特性，包括减少炎症和抑制铜绿假单胞菌的毒力。AZM作为抗p的潜力很大。本文提出了将特洛伊木马策略应用于AZM衍生物的合成。本研究设计并合成了儿茶酚偶联AZM衍生物，并对其抗p活性进行了评价。绿脓杆菌的活动。其中一种衍生物对AZM具有较好的抑菌活性，甚至对耐多药铜绿假单胞菌临床分离株也具有抑菌活性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ChemMedChem 医学-药学

CiteScore

6.70

自引率

2.90%

发文量

280

审稿时长

1 months

期刊介绍： Quality research. Outstanding publications. With an impact factor of 3.124 (2019), ChemMedChem is a top journal for research at the interface of chemistry, biology and medicine. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies. ChemMedChem publishes primary as well as critical secondary and tertiary information from authors across and for the world. Its mission is to integrate the wide and flourishing field of medicinal and pharmaceutical sciences, ranging from drug design and discovery to drug development and delivery, from molecular modeling to combinatorial chemistry, from target validation to lead generation and ADMET studies. ChemMedChem typically covers topics on small molecules, therapeutic macromolecules, peptides, peptidomimetics, and aptamers, protein-drug conjugates, nucleic acid therapies, and beginning 2017, nanomedicine, particularly 1) targeted nanodelivery, 2) theranostic nanoparticles, and 3) nanodrugs. Contents ChemMedChem publishes an attractive mixture of: Full Papers and Communications Reviews and Minireviews Patent Reviews Highlights and Concepts Book and Multimedia Reviews.