{"title":"吡啶基杂环肼:具有高效抗菌活性的跨膜 H+/Cl- Symporters。","authors":"Abhishek Mondal, Manisha Siwach, Manzoor Ahmad, Sunish Kumar Radhakrishnan and Pinaki Talukdar*, ","doi":"10.1021/acsinfecdis.3c00455","DOIUrl":null,"url":null,"abstract":"<p >The development of potent antibacterial agents has become increasingly difficult as bacteria continue to evolve and develop resistance to antibiotics. It is therefore imperative to find effective antimicrobial agents that can address the evolving challenges posed by infectious diseases and antimicrobial resistance. Using artificial transmembrane ion transporters is an emerging and promising avenue to address this issue. We report pyridyl-linked hetero hydrazones as highly efficient transmembrane HCl symporters. These compounds offer an appropriate HCl binding site through cooperative protonation, followed by recognition of chloride ions. HCl transport by these compounds inhibits the growth of different Gram-negative bacterial strains with high efficacy by affecting the cell envelope homeostasis. This specific class of compounds holds substantial promise in the ongoing pursuit of developing highly efficient antibacterial agents.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":"10 2","pages":"371–376"},"PeriodicalIF":3.8000,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Pyridyl-Linked Hetero Hydrazones: Transmembrane H+/Cl– Symporters with Efficient Antibacterial Activity\",\"authors\":\"Abhishek Mondal, Manisha Siwach, Manzoor Ahmad, Sunish Kumar Radhakrishnan and Pinaki Talukdar*, \",\"doi\":\"10.1021/acsinfecdis.3c00455\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >The development of potent antibacterial agents has become increasingly difficult as bacteria continue to evolve and develop resistance to antibiotics. It is therefore imperative to find effective antimicrobial agents that can address the evolving challenges posed by infectious diseases and antimicrobial resistance. Using artificial transmembrane ion transporters is an emerging and promising avenue to address this issue. We report pyridyl-linked hetero hydrazones as highly efficient transmembrane HCl symporters. These compounds offer an appropriate HCl binding site through cooperative protonation, followed by recognition of chloride ions. HCl transport by these compounds inhibits the growth of different Gram-negative bacterial strains with high efficacy by affecting the cell envelope homeostasis. This specific class of compounds holds substantial promise in the ongoing pursuit of developing highly efficient antibacterial agents.</p>\",\"PeriodicalId\":17,\"journal\":{\"name\":\"ACS Infectious Diseases\",\"volume\":\"10 2\",\"pages\":\"371–376\"},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2024-01-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Infectious Diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acsinfecdis.3c00455\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Infectious Diseases","FirstCategoryId":"3","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acsinfecdis.3c00455","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Pyridyl-Linked Hetero Hydrazones: Transmembrane H+/Cl– Symporters with Efficient Antibacterial Activity
The development of potent antibacterial agents has become increasingly difficult as bacteria continue to evolve and develop resistance to antibiotics. It is therefore imperative to find effective antimicrobial agents that can address the evolving challenges posed by infectious diseases and antimicrobial resistance. Using artificial transmembrane ion transporters is an emerging and promising avenue to address this issue. We report pyridyl-linked hetero hydrazones as highly efficient transmembrane HCl symporters. These compounds offer an appropriate HCl binding site through cooperative protonation, followed by recognition of chloride ions. HCl transport by these compounds inhibits the growth of different Gram-negative bacterial strains with high efficacy by affecting the cell envelope homeostasis. This specific class of compounds holds substantial promise in the ongoing pursuit of developing highly efficient antibacterial agents.
期刊介绍:
ACS Infectious Diseases will be the first journal to highlight chemistry and its role in this multidisciplinary and collaborative research area. The journal will cover a diverse array of topics including, but not limited to:
* Discovery and development of new antimicrobial agents — identified through target- or phenotypic-based approaches as well as compounds that induce synergy with antimicrobials.
* Characterization and validation of drug target or pathways — use of single target and genome-wide knockdown and knockouts, biochemical studies, structural biology, new technologies to facilitate characterization and prioritization of potential drug targets.
* Mechanism of drug resistance — fundamental research that advances our understanding of resistance; strategies to prevent resistance.
* Mechanisms of action — use of genetic, metabolomic, and activity- and affinity-based protein profiling to elucidate the mechanism of action of clinical and experimental antimicrobial agents.
* Host-pathogen interactions — tools for studying host-pathogen interactions, cellular biochemistry of hosts and pathogens, and molecular interactions of pathogens with host microbiota.
* Small molecule vaccine adjuvants for infectious disease.
* Viral and bacterial biochemistry and molecular biology.