Shabin N. Chathangad, Vishnu N. Vijayan, Jissy Anna George and Sushabhan Sadhukhan*,
{"title":"基于1,2,3-三唑的多模态抗菌药物的Click化学策略设计","authors":"Shabin N. Chathangad, Vishnu N. Vijayan, Jissy Anna George and Sushabhan Sadhukhan*, ","doi":"10.1021/acsbiomedchemau.4c00132","DOIUrl":null,"url":null,"abstract":"<p >Drug-resistant bacterial infections impose a major threat to human health, as current antibiotic treatments are becoming increasingly ineffective. Priority has been given to the development of alternative medications to curb the development of resistance or agents that can work on the resistance strains. Among various promising approaches, 1,2,3-triazole-based molecular hybrids have emerged as excellent candidates owing to their ease of synthesis, high structural diversity, functional tunability, and biocompatibility. The rapid advancement of biological understanding of 1,2,3-triazole has been greatly aided by the discovery of the Click reaction. Drugs with a single molecular target often fail to kill the bacteria effectively, and even if they do, the bacteria eventually become resistant by virtue of mutations or other mechanisms. In this context, the 1,2,3-triazole group has been explored to design novel molecular hybrids to combat antimicrobial resistance in an effective manner. Different types of 1,2,3-triazole-based hybrids have been developed that have shown inhibitory effects on critical bacterial enzymes, the ability to produce intracellular reactive oxygen species, and the ability to disrupt the cell membrane. Herein, we discuss the strategic design principles of triazole-based hybrids, their antibacterial potential, especially focusing on the drug resistance issue, and future perspectives to critically assess their potential for multitargeting antibacterial agents. The presented information can lead to the development of novel multifaceted antibacterial agents in the future by means of their unique chemical features to address the growing challenge of drug resistance.</p>","PeriodicalId":29802,"journal":{"name":"ACS Bio & Med Chem Au","volume":"5 4","pages":"486–504"},"PeriodicalIF":4.3000,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsbiomedchemau.4c00132","citationCount":"0","resultStr":"{\"title\":\"Mitigating Antimicrobial Resistance through Strategic Design of Multimodal Antibacterial Agents Based on 1,2,3-Triazole with Click Chemistry\",\"authors\":\"Shabin N. Chathangad, Vishnu N. Vijayan, Jissy Anna George and Sushabhan Sadhukhan*, \",\"doi\":\"10.1021/acsbiomedchemau.4c00132\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Drug-resistant bacterial infections impose a major threat to human health, as current antibiotic treatments are becoming increasingly ineffective. Priority has been given to the development of alternative medications to curb the development of resistance or agents that can work on the resistance strains. Among various promising approaches, 1,2,3-triazole-based molecular hybrids have emerged as excellent candidates owing to their ease of synthesis, high structural diversity, functional tunability, and biocompatibility. The rapid advancement of biological understanding of 1,2,3-triazole has been greatly aided by the discovery of the Click reaction. Drugs with a single molecular target often fail to kill the bacteria effectively, and even if they do, the bacteria eventually become resistant by virtue of mutations or other mechanisms. In this context, the 1,2,3-triazole group has been explored to design novel molecular hybrids to combat antimicrobial resistance in an effective manner. Different types of 1,2,3-triazole-based hybrids have been developed that have shown inhibitory effects on critical bacterial enzymes, the ability to produce intracellular reactive oxygen species, and the ability to disrupt the cell membrane. Herein, we discuss the strategic design principles of triazole-based hybrids, their antibacterial potential, especially focusing on the drug resistance issue, and future perspectives to critically assess their potential for multitargeting antibacterial agents. The presented information can lead to the development of novel multifaceted antibacterial agents in the future by means of their unique chemical features to address the growing challenge of drug resistance.</p>\",\"PeriodicalId\":29802,\"journal\":{\"name\":\"ACS Bio & Med Chem Au\",\"volume\":\"5 4\",\"pages\":\"486–504\"},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2025-03-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://pubs.acs.org/doi/pdf/10.1021/acsbiomedchemau.4c00132\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Bio & Med Chem Au\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acsbiomedchemau.4c00132\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Bio & Med Chem Au","FirstCategoryId":"1085","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acsbiomedchemau.4c00132","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Mitigating Antimicrobial Resistance through Strategic Design of Multimodal Antibacterial Agents Based on 1,2,3-Triazole with Click Chemistry
Drug-resistant bacterial infections impose a major threat to human health, as current antibiotic treatments are becoming increasingly ineffective. Priority has been given to the development of alternative medications to curb the development of resistance or agents that can work on the resistance strains. Among various promising approaches, 1,2,3-triazole-based molecular hybrids have emerged as excellent candidates owing to their ease of synthesis, high structural diversity, functional tunability, and biocompatibility. The rapid advancement of biological understanding of 1,2,3-triazole has been greatly aided by the discovery of the Click reaction. Drugs with a single molecular target often fail to kill the bacteria effectively, and even if they do, the bacteria eventually become resistant by virtue of mutations or other mechanisms. In this context, the 1,2,3-triazole group has been explored to design novel molecular hybrids to combat antimicrobial resistance in an effective manner. Different types of 1,2,3-triazole-based hybrids have been developed that have shown inhibitory effects on critical bacterial enzymes, the ability to produce intracellular reactive oxygen species, and the ability to disrupt the cell membrane. Herein, we discuss the strategic design principles of triazole-based hybrids, their antibacterial potential, especially focusing on the drug resistance issue, and future perspectives to critically assess their potential for multitargeting antibacterial agents. The presented information can lead to the development of novel multifaceted antibacterial agents in the future by means of their unique chemical features to address the growing challenge of drug resistance.
期刊介绍:
ACS Bio & Med Chem Au is a broad scope open access journal which publishes short letters comprehensive articles reviews and perspectives in all aspects of biological and medicinal chemistry. Studies providing fundamental insights or describing novel syntheses as well as clinical or other applications-based work are welcomed.This broad scope includes experimental and theoretical studies on the chemical physical mechanistic and/or structural basis of biological or cell function in all domains of life. It encompasses the fields of chemical biology synthetic biology disease biology cell biology agriculture and food natural products research nucleic acid biology neuroscience structural biology and biophysics.The journal publishes studies that pertain to a broad range of medicinal chemistry including compound design and optimization biological evaluation molecular mechanistic understanding of drug delivery and drug delivery systems imaging agents and pharmacology and translational science of both small and large bioactive molecules. Novel computational cheminformatics and structural studies for the identification (or structure-activity relationship analysis) of bioactive molecules ligands and their targets are also welcome. The journal will consider computational studies applying established computational methods but only in combination with novel and original experimental data (e.g. in cases where new compounds have been designed and tested).Also included in the scope of the journal are articles relating to infectious diseases research on pathogens host-pathogen interactions therapeutics diagnostics vaccines drug-delivery systems and other biomedical technology development pertaining to infectious diseases.