1,2,4‐Triazole hybrids with potential antibacterial activity against methicillin‐resistant Staphylococcus aureus

Methicillin‐resistant Staphylococcus aureus (MRSA) has developed numerous mechanisms of virulence and strategies to evade the human immune system, and it can be transmitted between humans, animals, and the environment. Thus, MRSA is an important cause of morbidity and mortality in both hospitals and in the community, creating an urgent demand for the development of novel anti‐MRSA candidates. The 1,2,4‐triazole nucleus is a bioisostere of amide, ester, and carboxylic acid, and the 1,2,4‐triazole ring is found in many compounds with diverse biological effects. 1,2,4‐Triazole derivatives could exert their antibacterial activity through inhibition of efflux pumps, filamentous temperature‐sensitive protein Z, penicillin‐binding protein, DNA gyrase, and topoisomerase IV, and they play an important role in the discovery of novel antibacterial agents. Among them, 1,2,4‐triazole hybrids, which have the potential to exert dual/multiple mechanisms of action, possess a promising broad‐spectrum antibacterial activity against a panel of clinically important drug‐resistant pathogens including MRSA. This review outlines the recent developments of 1,2,4‐triazole hybrids with a potential anti‐MRSA activity, covering articles published between 2010 and 2020. The mechanisms of action, critical aspects of their design, and structure–activity relationships are also discussed.