Harnessing Chemical Diversity to Disarm Bacterial Communication for 25 Years: Natural Products, Repurposed Drugs, Peptides, and Synthetic Quorum Sensing Inhibitors

IF 3.4 4区 医学 Q2 CHEMISTRY, MEDICINAL
ChemMedChem Pub Date : 2025-08-13 DOI:10.1002/cmdc.202500477
Tung Truong-Thanh, Anh Nguyen Phuong, Linh Nguyen Khanh, Duc Nguyen Minh
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引用次数: 0

Abstract

Quorum sensing, a bacterial communication pathway, has emerged as a promising target for the development of alternative antimicrobial agents in the battle against bacterial resistance. In addition to biological investigations of quorum sensing mechanisms, substantial efforts have been made towards the rational design, synthesis, identification of natural products, and screening of commercial drugs towards this target. There are several individual reviews on the discovery of quorum sensing inhibitors; however, there has yet to be a comprehensive, detailed, and critical review providing a complete overview of the development of novel quorum sensing inhibitors, ranging from natural compounds, peptides, and repurposed drugs to synthetic molecules. This review provides a comprehensive and critical overview of quorum sensing inhibitors, highlighting key advances in their discovery, structure–activity relationships, and mechanisms of action over the past 25 years (2000–2025). It emphasizes several FDA-approved drugs (e.g., azithromycin, ciprofloxacin, and paracetamol), natural compounds (e.g., ajoene, curcumin, quercetin, and carvacrol), peptides, and synthetic libraries that exhibit potent anti-QS and antibiofilm activities against pathogenic bacteria. Furthermore, a systematic structural comparison and potential strategies for developing next-generation therapeutics based on current advancements will be discussed.

Abstract Image

利用化学多样性解除细菌交流25年:天然产物,重新利用药物,肽和合成群体感应抑制剂。
群体感应作为一种细菌交流途径,已成为开发抗细菌耐药性替代抗菌药物的一个有希望的目标。除了群体感应机制的生物学研究外,针对这一目标的天然产物的合理设计、合成、鉴定和商业药物的筛选也做出了大量的努力。关于群体感应抑制剂的发现,有几篇单独的综述;然而,对于新型群体感应抑制剂的发展,从天然化合物、多肽、再用途药物到合成分子,尚未有一个全面、详细和批判性的综述。本综述对群体感应抑制剂进行了全面和批判性的概述,重点介绍了过去25年(2000-2025)中群体感应抑制剂的发现、构效关系和作用机制的关键进展。它强调了几种fda批准的药物(如阿奇霉素、环丙沙星和扑热息痛)、天然化合物(如阿琼烯、姜黄素、槲皮素和香芹酚)、肽和合成文库,它们对致病菌具有有效的抗qs和抗生物膜活性。此外,还将讨论基于当前进展的系统结构比较和开发下一代治疗方法的潜在策略。
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来源期刊
ChemMedChem
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.
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