α -amylase inhibition and in silico studies of novel naphtho[2,3- d ]imidazole-4,9-dione linked N -acyl hydrazones.

Aim: To enrich the pool of α -amylase inhibitors to manage Type 2 diabetes. Methods: Synthesis, conformational study, α -amylase inhibitory action and various in silico studies of novel N' -(arylbenzylidene)-2-(4,9-dioxo-4,9-dihydro-1 H -naphtho[2,3- d ]imidazol-1-yl)acetohydrazides carried out. Results: Compound H6 demonstrated the highest activity (IC 50  = 0.0437 μmol mL -1 ) among the tested compounds. Structure-activity relationship study suggested that variable substitution at the aryl ring has a pivotal role in determining the inhibitory action of tested compounds. Docking simulations of the most active compound ( H6 ) confirmed its interaction potential with active site residues of A. oryzae α -amylase. The root-mean-square deviation fluctuations substantiated the stability of protein-ligand complex. Absorption, distribution, metabolism and excretion prediction revealed optimal values for absorption, distribution, metabolism and excretion parameters. Conclusion: The developed molecules could be beneficial for the development of novel α -amylase inhibitors to treat Type 2 diabetes.