Indoles in drug design and medicinal chemistry

Abstract

Indole derivatives represent a significant class of compounds in medicinal chemistry due to their diverse biological activities and structural versatility. These compounds are central to the design of drugs targeting a wide array of diseases, including cancer, diabetes, cardiovascular disorders, neurological diseases, and infections. The indole scaffold facilitates interactions with biological macromolecules, enhancing its utility in drug development. This review summarizes the latest advancements in the synthesis, biological efficacy, and therapeutic potential of indole derivatives. Classical methods, such as Fischer, Bartoli, and Reissert indole synthesis, continue to serve as foundational techniques, while modern advancements in combinatorial methods, transition-metal catalysis, cyclization methods, nanoparticles-mediated synthesis, heterogenous catalysis, microwave-aided catalysis, ultrasound-aided approach, and green chemistry offer more efficient, sustainable approaches. Notably, indole derivatives exhibit potent antifungal, antiprotozoal, antidiabetic, antioxidant, antimalarial, antibacterial, anti-inflammatory, and anticancer activities. Recent studies highlight the role of structural modifications in optimizing these compounds for enhanced pharmacological outcomes. For instance, indole-triazole conjugates show impressive antifungal activity, while indole-thiazolidine-2,4-dione inhibitors exhibit strong antidiabetic effects. Additionally, indole derivatives have demonstrated efficacy in targeting key oncogenic pathways, with some compounds exhibiting potent anticancer properties against various cell lines. These promising findings are supported by computational modelling studies that reveal strong interactions with target proteins. Emerging trends in indole-based drug discovery, including the integration of computational modelling and molecular docking, are expected to drive the development of next-generation therapeutics. As research in this area progresses, indole derivatives are poised to remain integral to the development of innovative treatments for a broad range of diseases.