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

Yusuf Syaril Alam(1), Pratiwi Pudjiastuti(2*), Saipul Maulana(3), Nur Rahmayanti Afifah(4), Fahimah Martak(5), Arif Fadlan(6), Tutik Sri Wahyuni(7), Syukri Arief(8)

(1) Department of Chemistry, Faculty of Science and Data Analytics, Institut Teknologi Sepuluh Nopember, Jl. Arif Rahman Hakim, Surabaya 60115, Indonesia
(2) Department of Chemistry, Faculty of Science and Technology, Airlangga University, Surabaya 60115, Indonesia
(3) Department of Pharmaceutical Science, Faculty of Pharmacy, Airlangga University, Surabaya 60115, Indonesia
(4) Department of Chemistry, Faculty of Science and Data Analytics, Institut Teknologi Sepuluh Nopember, Jl. Arif Rahman Hakim, Surabaya 60115, Indonesia
(5) Department of Chemistry, Faculty of Science and Data Analytics, Institut Teknologi Sepuluh Nopember, Jl. Arif Rahman Hakim, Surabaya 60115, Indonesia
(6) Department of Chemistry, Faculty of Science and Data Analytics, Institut Teknologi Sepuluh Nopember, Jl. Arif Rahman Hakim, Surabaya 60115, Indonesia
(7) Department of Pharmaceutical Science, Faculty of Pharmacy, Airlangga University, Surabaya 60115, Indonesia
(8) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Andalas University, Limau Manis Campus, Padang 25163, Indonesia
(*) Corresponding Author


Two new of N’-benzylidenebenzohydrazide (NBB) derivatives were successfully synthesized and yielded 5058%. FTIR, ESI-MS, 1H-NMR and 13C-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.


N’-Benzylidenebenzohydrazide; α-amylase; derivatives; antidiabetic; In silico

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