Triazole and Thiadiazole Heterocyclic derivatives: Review on Chemistry, Synthetic Strategies and Antidiabetic evaluation.

Author

Ms. Rameema R, Dr. Sebastin V


Abstract

 Diabetes mellitus continues to rank among the most serious public health challenges worldwide, as the number of people affected keeps increasing steadily across nearly all regions and age groups. Against this broader backdrop, type 2 diabetes mellitus (T2DM) represents most cases and is the primary contributor to this expanding burden; current estimates indicate that 589 million adults are affected globally, with this number expected to approach 900 million by 2050. Inhibiting the digestive enzymes alpha-amylase and alpha-glucosidase to control postprandial blood sugar elevations remains a key approach in oral antidiabetic treatment, yet the currently approved inhibitors — acarbose, miglitol and voglibose — are sugar-like compounds, and their digestive side effects restrict patients’ long-term tolerance. Consequently, continued attention has focused on non-sugar heterocyclic inhibitors, especially those based on triazole and 1,3,4-thiadiazole rings, as well as their fused triazolo-thiadiazole hybrids. This review uses the primary medicinal-chemistry literature to outline the chemical rationale for these scaffolds, representative synthetic pathways, structure–activity relationships obtained from laboratory alpha-amylase/alpha-glucosidase assays, enzyme-kinetic and computational-docking studies, and other antidiabetic-relevant targets, including aldose reductase. Throughout the reviewed research, halogen substitution, hydrogen-bond-donating groups and rigid fused ring systems repeatedly emerge as advantageous design characteristics, while several compounds demonstrate nanomolar-to-low-micromolar potency against one or both enzymes. The review concludes by assessing the strength of the available evidence and the remaining work required before these compounds can potentially advance to clinical use. 


Keywords

type 2 diabetes; alpha-glucosidase; alpha-amylase; triazole; thiadiazole; triazolo-thiadiazole



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References


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