Mitigating Antimicrobial Resistance through Strategic Design of Multimodal Antibacterial Agents Based on 1,2,3-Triazole with Click Chemistry

IF 4.3 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Shabin N. Chathangad, Vishnu N. Vijayan, Jissy Anna George and Sushabhan Sadhukhan*, 
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引用次数: 0

Abstract

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.

基于1,2,3-三唑的多模态抗菌药物的Click化学策略设计
耐药细菌感染对人类健康构成重大威胁,因为目前的抗生素治疗越来越无效。优先考虑的是开发替代药物,以遏制耐药性的发展或可以对耐药菌株起作用的药物。在各种有前途的方法中,1,2,3-三唑基分子杂化物因其易于合成、结构多样性高、功能可调性和生物相容性而成为极好的候选。Click反应的发现极大地促进了对1,2,3-三唑的生物学认识的快速发展。具有单一分子靶标的药物往往不能有效地杀死细菌,即使它们这样做,细菌最终也会凭借突变或其他机制产生抗药性。在这种情况下,1,2,3-三唑基团已被探索设计新的分子杂交以有效地对抗抗菌素耐药性。不同类型的1,2,3-三唑基杂合物已经被开发出来,它们显示出对关键细菌酶的抑制作用,产生细胞内活性氧的能力,以及破坏细胞膜的能力。在此,我们讨论了基于三唑的杂交种的策略设计原则,它们的抗菌潜力,特别是耐药性问题,以及未来的观点,以批判性地评估它们作为多靶向抗菌剂的潜力。所提供的信息可以通过其独特的化学特性导致未来新型多面抗菌药物的开发,以解决日益增长的耐药性挑战。
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来源期刊
ACS Bio & Med Chem Au
ACS Bio & Med Chem Au 药物、生物、化学-
CiteScore
4.10
自引率
0.00%
发文量
0
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.
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