Carbazole: A Versatile Scaffold in Medicinal Chemistry – A Review on the Synthesis and Antimicrobial Evaluation of New Derivatives

The relentless rise of antimicrobial resistance (AMR) poses a grave threat to global public health, necessitating the urgent discovery of novel therapeutic agents with new mechanisms of action. Nitrogen-containing heterocycles have long been recognized as privileged structures in drug discovery due to their diverse biological activities. Among them, the carbazole nucleus, a tricyclic aromatic system comprising two benzene rings fused on either side of a pyrrole ring, has emerged as a highly promising scaffold. Carbazole derivatives are widely distributed in nature and have demonstrated a broad spectrum of pharmacological properties, including significant antimicrobial activity. This review systematically consolidates and critically evaluates the recent advancements (from approximately 2015 to the present) in the design, synthesis, and antimicrobial evaluation of new carbazole-based derivatives. We delve into various synthetic strategies, ranging from classical methods like the Bischler-Napieralski and Graebe-Ullmann reactions to modern transition-metal-catalyzed approaches for constructing the carbazole core and its functionalized analogues. A major focus is placed on the structure-activity relationship (SAR) studies, elucidating how different substituents—such as halogens, nitro groups, amino groups, and various heterocyclic hybrids—influence the potency and spectrum of activity against a panel of pathogenic bacteria and fungi. The review also discusses the potential mechanisms of action, including DNA intercalation, inhibition of efflux pumps, and disruption of microbial cell membranes. Finally, we address the current challenges and future perspectives for developing carbazole derivatives as a new class of clinically viable antimicrobial agents to combat the escalating AMR crisis.