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

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.

Keywords:

• Pyrazole
• hydrazone
• DFT
• anticancer
• proylendopeptidase
• α-glucosidase
• molecular docking

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research was partially supported by UM5R. BEB would thank Mrs Sadia Siddiq (Manager, Molecular Bank, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi -75270, Pakistan) for the help in realizing the biological tests. YS would like to thank Prof. Dr. Fatih Ucun for his helpful contribution and Gaussian Calculations.