Aziridine as Emerging Scaffold: Focusing on Anti-diabetic Perspectives

Aziridine, a three-membered nitrogen-containing heterocycle, has gained significant attention as a versatile scaffold in drug discovery due to its unique reactivity and structural rigidity. Its strained ring system allows for facile derivatization, enabling the synthesis of a wide range of bioactive molecules. In recent years, aziridine-based compounds have been explored for their potential in treating diabetes mellitus, a chronic metabolic disorder characterized by impaired glucose homeostasis. Several studies have highlighted the role of aziridine derivatives in modulating key molecular targets involved in diabetes, such as dipeptidyl peptidase-4 (DPP-4), α-glucosidase, aldose reductase, and peroxisome proliferator-activated receptors (PPARs). Additionally, aziridine scaffolds have demonstrated promising inhibitory activity against advanced glycation end-products (AGEs), which play a crucial role in diabetic complications. The ability of aziridine derivatives to enhance insulin sensitivity, improve glucose uptake, and regulate oxidative stress further strengthens their therapeutic potential. Moreover, their ease of synthetic modifications allows for fine-tuning of pharmacokinetic and pharmacodynamic properties, improving bioavailability and target selectivity. This review aims to provide a comprehensive insight into the recent advancements in aziridine-based anti-diabetic agents, focusing on their various synthetic routes, mechanistic approaches, structure-activity relationships, and future perspectives. By elucidating the potential of aziridine as a promising scaffold, this study underscores its significance in the development of novel therapeutic agents for diabetes management.