Harnessing Transition Metal Scaffolds for Targeted Antibacterial Therapy

Antimicrobial resistance, caused by persistent adaptation and growing resistance of pathogenic bacteria to overprescribed antibiotics, poses one of the most serious and urgent threats to global public health. The limited pipeline of experimental antibiotics in development further exacerbates this looming crisis and new drugs with alternative modes of action are needed to tackle evolving pathogenic adaptation. Transition metal complexes can replenish this diminishing stockpile of drug candidates by providing compounds with unique properties that are not easily accessible using pure organic scaffolds. We spotlight four emerging strategies to harness these unique properties to develop new targeted antibacterial agents. Antimicrobial resistance is one of the most serious threats to public health but the problem is compounded by the lack of new drugs with new modes of action in the development pipeline. In this review, we spotlight four emerging antibacterial strategies that take advantages of the unique chemical properties of transition metal complexes, namely Trojan horse, triggered warhead release, "new-to-nature" chemistry, and biomimetic reactions. We further propose that transition metal complexes can replenish this diminishing stockpile of drug candidates by providing compounds with unique properties that are not easily accessible using pure organic scaffolds.image