Structure and Target‐Based Insights into the Antimicrobial Potential of 1,4‐Dihydropyridine Derivatives

Abstract

Antimicrobial resistance (AMR) represents a critical global health crisis, eroding the efficacy of conventional therapies and necessitating the urgent discovery of novel agents with an innovative mechanism of action. A privileged structure in medicinal chemistry, the 1,4‐dihydropyridine (1,4‐DHP) scaffold has shown great promise for the development of antimicrobial drugs in addition to its well‐established use in cardiovascular medicine. This review emphasizes how 1,4‐DHP derivatives have a great deal of promise as adaptable next‐generation antibiotics. We examine the various modes of action, which include the inhibition of vital bacterial enzymes and strong antibiofilm and antifungal effects by targeting various targets. Furthermore, we provide an overview of the number of potent 1,4‐DHP derivatives that have been recently documented in the literature, describing their broad‐spectrum effectiveness against a variety of bacterial and fungal pathogens that are resistant to multiple drugs. Strategic changes at C‐3, C‐5, and especially the C‐4 position of the dihydropyridine ring are essential for improving potency and spectrum. In conclusion, the 1,4‐DHP scaffold provide a promising framework for the design of new antimicrobial agents that exploit multi‐target and anti‐virulence strategies, although substantial in vivo and clinical validation remains necessary.