1,3-Thiazole nucleus as promising molecular platform against antimicrobial resistance: a recent overview in drug discovery

Abstract

Antimicrobial resistance (AMR) has emerged as one of the foremost public health threats of the 21st century. The progressive decline in the efficacy of conventional antibiotics, combined with a scarcity of new drug classes approved in recent decades, has created a critical and alarming scenario. In this context, new biological, chemical, and artificial intelligence tools have played a fundamental role in supporting the discovery of compounds aimed at improving safety, efficacy, and broad-spectrum activity, addressing both AMR and the high costs associated with drug development. Recent data from the World Health Organization (WHO) highlight a list of priority pathogens intended to guide efforts in the search for new therapeutic options. Most compounds currently in preclinical and clinical development are small molecules with direct mechanisms of action. Within this landscape, the search for new molecular scaffolds has focused especially on derivatives of natural compounds and synthetic heterocyclic structures. Among these, derivatives containing the 1,3-thiazole core have stood out due to their synthetic versatility and ability to interact with various bacterial molecular targets. This review provides a comprehensive overview of different classes of thiazole derivatives with demonstrated activity against multidrug-resistant bacterial strains. Their mechanisms of action, relevant chemical, and pharmacological properties, as well as methodological approaches applied to the discovery of these bioactive compounds are discussed highlighting their potential in the development of new therapeutic alternatives to combat bacterial resistance.

Keywords: 1,3-Thiazole; Antibacterial agents; Bacterial resistance; Drug design; Structure-activity relationship (SAR).