ABSTRACT The escalating crisis of bacterial resistance demands the urgent discovery of novel antibacterial agents. The natural product kojic acid has emerged as a privileged pharmacophore for developing new antibacterial and antibiofilm agents, owing to its excellent metal‐chelating properties and structural versatility. This review aims to provide recent advances in kojic acid‐based derivatives as antibacterial and antibiofilm agents, docking studies, mechanisms of action, and structure‐activity relationships, with emphasis on key optimization strategies such as Mannich base formation, iron‐chelation design, and hybrid conjugation with antibiotics. We discussed the action mechanism of derivatives and antibacterial activity of derivatives against pathogens, including Gram‐positive strains (such as Staphylococcus aureus ) and Gram‐negative strains (such as Pseudomonas aeruginosa ). SARs reveal that the introduction of hydrophobic moieties at the C‐6 position of the hydroxypyranone core is crucial for enhancing activity against gram‐positive bacteria, while modifications at the C‐2 position or the hydroxyl groups primarily influence metal coordination and antibiofilm efficacy. Collectively, we address the current challenges and future directions for this promising class of compounds, offering valuable insights for the rational design of potent antibacterial and antibiofilm agents based on the kojic acid scaffold.
Wang et al. (Wed,) studied this question.