Antimicrobial Activity of Lipophilic Gallium-Based Compounds: An Emerging Frontier in Metal-Based Antimicrobials

Antimicrobial resistance (AMR) is an increasing global health threat that underscores the urgent need for antimicrobial agents with mechanisms of action distinct from those of conventional antibiotics. Gallium (Ga) has emerged as a promising metal-based antimicrobial owing to the chemical similarity of Ga(III) to Fe(III), which enables it to interfere with bacterial iron acquisition and utilization. In contrast to Fe(III), Ga(III) is redox-inactive under physiological conditions and cannot support the redox reactions required for many iron-dependent cellular processes, thereby disrupting bacterial metabolism. This review highlights recent advances in gallium-based antimicrobial strategies, with particular emphasis on the role of ligand coordination in modulating the antibacterial activity of Ga(III) against drug-resistant pathogens. Emerging evidence indicates that coordination with lipophilic ligands can enhance the cellular update and accumulation of Ga(III) and may confer additional antibacterial effects beyond Fe(III) mimicry alone. These findings suggest that ligand design is a key strategy for tuning the physicochemical properties and antimicrobial activity of gallium complexes. Rational development of ligand-coordinated Ga(III) complexes may therefore provide new therapeutic approaches for combating multidrug-resistant bacterial infections.