Target based synthesis, medicinal evaluation and in silico modeling of thiazole incorporating bis-Schiff bases: Ligands protein interaction against α amylase and α glucosidase insight

Thiazole based compounds have strong anti-diabetic potential. In order to treat diabetes mellitus, thiazole based bis-Schiff base derivatives were synthesized in the present research work. All of the synthesized compounds were structurally analyzed via 13C NMR, 1H NMR, as well as HREI-MS. Biological profile of all the compounds was assessed to explore effective anti-diabetic therapeutic agent in comparison to reference drug acarbose. Analogue 4 with IC50 = 1.50 +/- 0.40 and 2.60 +/- 0.30 mu M against alpha-amylase and alpha-glucosidase emerged as leading drug candidate with excellent inhibition. The trifluoromethyl moiety in analogue 4 engages enzyme's active site via a hydrogen bonding. Molecular docking investigation provided insight into binding interactions of potent compounds with target enzymes and arene-arene, arene-H and arene-cation interactions were visualized for potent compounds against target enzymes. Moreover, the ADME analysis was used to investigate drug-like characteristics of lead compounds.