Structure-Activity Relationship of Hydrazinylthiazole-5-Carbaldehydes as Potential Anti-Diabetic Agents.

Diabetes is an emerging threat to the world due to large number of deaths reported within the last decade. To overcome its spread and complications, herein, we reported synthesis and anti-diabetic potential of twelve novel 2-[(arylidenyl)methylidene]hydrazinyl-1,3-thiazole-5-carbaldehydes (3 a-l). All compounds have shown good to excellent α-amylase inhibitory activity, among them ortho substituted analogues, the compound 3 a (IC ₅₀ =14.6 mM) and 3 l (IC ₅₀ =17.9 mM) showed excellent inhibition potential due to the strong electron donating nature of the substituents attached at the aryl ring. The compounds 3 a-3 h (IC ₅₀ =6.70-10.80 ppm) exhibited excellent anti-glycation potential as compared to standard amino-guanidine (IC ₅₀ =11.92 ppm). Almost all the tested compounds are found biocompatible and very safe to the human erythrocyte cells at all tested concentrations. The molecular docking results have found that the binding energy score of all the tested compounds against human serum albumin protein (pdb: 1AO6) is between -5.1827 and -6.8661 kcal/mol which is far better than standard amino-guanidine (-4.234 kcal/mol).
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