A promising α-amylase inhibitor based on the 2-(2-hydrazinyl) thiazole scaffolds: synthesis, docking studies and biological evaluation

Abstract

A series of novel hydrazinyl-based thiazole scaffolds were designed, synthesized, and evaluated for their anti-diabetic activity. The cyclocondensation reaction of the appropriately substituted acetophenones 1, thiosemicarbazide 2, and appropriate phenacyl bromide 3 allowed for the creation of a new series of hydrazinyl-based thiazole scaffolds (4a–h). The newly generated compounds were characterized using mass spectrometry,¹H NMR, IR, and ¹³C NMR techniques. The novel hydrazinyl-based thiazole scaffolds were evaluated by the in vitro α-amylase inhibitory assay. Hydrazinyl-based thiazole scaffolds 4a, 4b, 4d, and 4f showed good activity compared to acarbose as a standard reference. Although insulin is a necessary medication for the treatment of diabetes, it carries a significant risk. We believe that thiazole scaffolds based on hydrazinyl structural motive provide recommendations for designing and producing novel anti-diabetic drugs, which are critically needed. Moreover, these compounds show a strong affinity for the pancreatic α-amylase protein binding site, suggesting greater inhibitory capability at the cellular level, and molecular docking studies have demonstrated their better-fit potential as anti-diabetic agents. This indicates the versatility of the hydrazinyl-based thiazole molecules to achieve new classes of anti-diabetic scaffold.