Three new N’-benzylidenebenzohydrazide (NBB) derivatives were successfully synthesized and yielded 50–58%. FTIR, ESI-MS,1H-and13C-NMR were used to investigate the characteristic of NBB derivates. The structure and relationship of NBB derivatives into α-glucosidase and α-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 (ΔGbind (MM-GBSA)) of NBB to α-glucosidase and α-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 α-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 α-glucosidase cavity as well as the native ones, including Ala281, Asp282, and Asp616. NBB and native ligand showed similar interaction between α-amylase with Gly110 amino acid residue.
- in silico