Indole–Imidazole Hybrids as Emerging Therapeutic Scaffolds: Synthetic Advances and Biomedical Applications

Abstract

Indole and imidazole structures are widely used in medicinal chemistry for their unique electronic, steric, and pharmacophoric qualities that drive diverse biological effects. Combining indole and imidazole structures enhanced structural diversity, binding affinity, making a promising approach for creating multifunctional therapeutic agents. This review presents a comprehensive overview of the synthetic strategies developed for indole–imidazole derivatives, encompassing multistep synthesis, one-pot multicomponent condensation reactions, metal-catalyzed reactions, metal-free catalysis, and various green chemistry approaches, with particular emphasis on efficiency, yields, and practical limitations. In addition, this review critically evaluates the biological activities of indole–imidazole scaffolds, highlighting their applications as anticancer, antioxidant, anti-microbial, neurological, and metabolic agents. By integrating recent synthetic advances with pharmacological insights, this review underscores both the opportunities and challenges in the hybrid design. It also provides direction for future research aimed at developing novel drug candidates to tackle current healthcare concerns such as antibiotic resistance, cancer, and chronic diseases.