Synthesis, α-Glucosidase Inhibition, Anticancer, DFT and Molecular Docking Investigations of Pyrazole Hydrazone Derivatives
Khalid Karrouchi, Yusuf Sert, M’hammed Ansar, Smaail Radi, Brahim El Bali, Rehan Imad, Anum Alam, Rimsha Irshad, Sheeba Wajid, Muhammad Altaf
Abstract
In this work, three N'-arylidene-5-phenyl-1H-pyrazole-3-carbohydrazide (3a-3c), derivatives have been synthesized and fully characterized by IR, 1H & 13C 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, 1H & 13C 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 α-glucosidase inhibitory activities. Compounds 3c showed significant anticancer activity against lung cancer cell line (H460) with the IC50 value 0.15 ± 0.01 µM. The other compounds exhibited prolyl endopeptidase (PEP) activity. Compounds 3a and 3c have demonstrated a potent α-glucosidase inhibitory activity with the IC50 value 360.4 ± 0.7 µM and 370.3 ± 1.17 µM, 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 μM and an active hydrogen bond to three.