Synthesis, alpha-Glucosidase Inhibition, Anticancer, DFT and Molecular Docking Investigations of Pyrazole Hydrazone Derivatives


Karrouchi K., SERT Y. , Ansar M., Radi S., El Bali B., Imad R., ...More

POLYCYCLIC AROMATIC COMPOUNDS, 2022 (Journal Indexed in SCI) identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2022
  • Doi Number: 10.1080/10406638.2022.2097275
  • Title of Journal : POLYCYCLIC AROMATIC COMPOUNDS
  • Keywords: Pyrazole, hydrazone, DFT, anticancer, proylendopeptidase, alpha-glucosidase, molecular docking, SELF-ASSEMBLY PROCESS, BIOLOGICAL EVALUATION, CRYSTAL-STRUCTURE, CYTOTOXICITY EVALUATION, SCALE FACTORS, SCHIFF-BASES, COMPLEXES, SIMULATIONS, ANTIOXIDANT, ACETAMIDE

Abstract

In this work, three N'-arylidene-5-phenyl-1H-pyrazole-3-carbohydrazide (3a-3c), derivatives have been synthesized and fully characterized by IR, H-1 & C-13 NMR and ESI-MS using experimental and theoretical methods. Theoretical calculations were carried out by DFT/B3LYP method using 6-311++G(d,p) basis set. For theoretical IR, H-1 & C-13 NMR (with GIAO method), MEP, HOMO-LUMO energies analyses of compounds 3a-3c were performed over the optimized structures. All newly synthesized compounds were screened for their cytotoxicity, proylenpeptidase and alpha-glucosidase inhibitory activities. Compounds 3c showed significant anticancer activity against lung cancer cell line (H460) with the IC50 value 0.15 +/- 0.01 mu M. The other compounds exhibited prolyl endopeptidase (PEP) activity. Compounds 3a and 3c have demonstrated a potent alpha-glucosidase inhibitory activity with the IC50 value 360.4 +/- 0.7 mu M and 370.3 +/- 1.17 mu M, respectively. Furthermore, in-silico based molecular docking study was performed between the title ligands and lung cancer cell line-H460 protein: 1M17. The best affinity bond was observed between compound 3c and the protein 1M17 with an energy of -8.6 (kcal/mol), an inhibition constant of 0.496769 mu M and an active hydrogen bond to three.