Synthesis and Antidiabetic Evaluation of N'-Benzylidenebenzohydrazide Derivatives by In Silico Studies

Three new N'-benzylidenebenzohydrazide (NBB) derivatives were successfully synthesized and yielded 50-58%. FTIR, ESI-MS,H-1-and C-13-NMR were used to investigate the characteristic of NBB derivates. The structure and relationship of NBB derivatives into a-glucosidase and a-amylase as good targets for diabetes treatment were evaluated using in silico screening. Molecular mechanics-Poisson Boltzmann/generalized born surface area (MM-PB/GBSA) was used to calculate the free binding energy (?(Gbind (MM-GBSA))) of NBB to a-glucosidase and a-amylase receptors showed that the results of - 0.45 and -20.79 kcal/mol, respectively. In the ortho position, NBB derivatives exhibited electron donating groups (EDG like-OCH3,-OH and-Cl with binding free energies of - 21.94, -6.71, and 21.94, respectively, and acarbose, a native ligand energy of -32.62 kcal/mol. In addition, the binding free energy of N-2-(-OCH3,-OH and-Cl)-NBB to the a-amylase receptor showed the number of -39.33, -43.96, -42.81, respectively and - 46.51 kcal/mol in comparing with a native ligand. As a result, it was found that all the NBB derivatives were able to interact with several amino acids in the a-glucosidase cavity as well as the native ones, including Ala281, Asp282, and Asp616. NBB and native ligand showed similar interaction between a-amylase with Gly110 amino acid residue.