1,2,3-Triazole-containing hybrids with potential antibacterial activity against ESKAPE pathogens

Area of Science:

• Medicinal Chemistry
• Antimicrobial Drug Discovery
• Organic Synthesis

Background:

• ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species) are leading causes of hospital-acquired infections, characterized by high morbidity, mortality, and increasing antibiotic resistance.
• The urgent need for novel therapeutics against multidrug-resistant bacteria necessitates exploration of alternative chemical scaffolds.
• 1,2,3-Triazole derivatives have emerged as versatile pharmacophores and linkers in drug design, demonstrating potential in various therapeutic areas.

Purpose of the Study:

• To review the recent (2018-2022) development of 1,2,3-triazole-containing hybrids with antibacterial activity against ESKAPE pathogens.
• To emphasize the potential of these compounds as viable prototypes for combating bacterial infections, including those caused by drug-resistant strains.
• To guide the rational design of more potent and effective antibacterial agents based on the 1,2,3-triazole scaffold.

Main Methods:

• Literature search and review of scientific publications from 2018 to 2022.
• Analysis of chemical structures and reported antibacterial activities of 1,2,3-triazole hybrids against ESKAPE pathogens.
• Synthesis and structure-activity relationship (SAR) studies of novel triazole derivatives were examined.

Main Results:

• Several 1,2,3-triazole-containing hybrids have demonstrated significant in vitro and in vivo antibacterial activity against various ESKAPE pathogens.
• Approved antibiotics like cefatrizine, radezolid, and tazobactam incorporate the 1,2,3-triazole moiety, validating its clinical utility.
• Recent studies showcase diverse synthetic strategies for generating novel triazole hybrids with improved efficacy and reduced toxicity.

Conclusions:

• 1,2,3-Triazole hybrids represent a promising class of compounds for the development of new antibiotics to address the challenge of ESKAPE pathogens and antimicrobial resistance.
• The established success of existing triazole-based drugs underscores the therapeutic potential of this scaffold.
• Continued research focusing on the rational design and synthesis of novel 1,2,3-triazole derivatives is crucial for advancing antibacterial drug discovery.