The discovery of novel antimicrobial peptides against drug-resistant bacteria based on fragments fusion strategy

IF 6 2区医学 Q1 CHEMISTRY, MEDICINAL

European Journal of Medicinal Chemistry Pub Date : 2025-03-08 DOI:10.1016/j.ejmech.2025.117493

Chunlan Zeng , Ziyao Ning , Yijie Xu , Long Tian , Jie Jing , Longming Chen , Weifeng Ye , Jiaqi Han , Taoran Wang , Zhao Meng , Qingbin Meng

{"title":"The discovery of novel antimicrobial peptides against drug-resistant bacteria based on fragments fusion strategy","authors":"Chunlan Zeng , Ziyao Ning , Yijie Xu , Long Tian , Jie Jing , Longming Chen , Weifeng Ye , Jiaqi Han , Taoran Wang , Zhao Meng , Qingbin Meng","doi":"10.1016/j.ejmech.2025.117493","DOIUrl":null,"url":null,"abstract":"<div><div>Since the escalating prevalence of multidrug-resistant (MDR) bacterial infections posing global health challenges, novel antimicrobial agents are urgently needed. This study designed a series of antimicrobial peptides by fusing two fragments of antimicrobial peptides sC18<sub>4b</sub> (1–9) and MSI-78 (10–16). Among these peptides, 13DK<sub>all</sub>Dab exhibited broad-spectrum antimicrobial efficacy against six different MDR bacterial strains with relatively low MICs. It exerted antibacterial effects through a membrane-disruption mechanism and maintained high stability in serum environment. Moreover, 13DK<sub>all</sub>Dab displayed low cytotoxicity and hemolysis <em>in vitro</em>, and significant therapeutic efficacy in a mouse acute peritonitis model. These findings demonstrate that 13DK<sub>all</sub>Dab is a promising antimicrobial agent in counteracting multidrug-resistant bacterial infections.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"289 ","pages":"Article 117493"},"PeriodicalIF":6.0000,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Medicinal Chemistry","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0223523425002582","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}

引用次数: 0

Abstract

Since the escalating prevalence of multidrug-resistant (MDR) bacterial infections posing global health challenges, novel antimicrobial agents are urgently needed. This study designed a series of antimicrobial peptides by fusing two fragments of antimicrobial peptides sC18_4b (1–9) and MSI-78 (10–16). Among these peptides, 13DK_allDab exhibited broad-spectrum antimicrobial efficacy against six different MDR bacterial strains with relatively low MICs. It exerted antibacterial effects through a membrane-disruption mechanism and maintained high stability in serum environment. Moreover, 13DK_allDab displayed low cytotoxicity and hemolysis in vitro, and significant therapeutic efficacy in a mouse acute peritonitis model. These findings demonstrate that 13DK_allDab is a promising antimicrobial agent in counteracting multidrug-resistant bacterial infections.

Abstract Image

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

European Journal of Medicinal Chemistry 化学-医药化学

CiteScore

11.70

自引率

9.00%

发文量

863

审稿时长

29 days

期刊介绍： The European Journal of Medicinal Chemistry is a global journal that publishes studies on all aspects of medicinal chemistry. It provides a medium for publication of original papers and also welcomes critical review papers. A typical paper would report on the organic synthesis, characterization and pharmacological evaluation of compounds. Other topics of interest are drug design, QSAR, molecular modeling, drug-receptor interactions, molecular aspects of drug metabolism, prodrug synthesis and drug targeting. The journal expects manuscripts to present the rational for a study, provide insight into the design of compounds or understanding of mechanism, or clarify the targets.