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Synthesis, Biological Evaluation, and QPLD Studies of Piperazine Derivatives as Potential DPP-IV Inhibitors

Author(s):

Reema Abu Khalaf*, Haya Abu Jarad, Tariq Al-Qirim and Dima Sabbah   Pages 1 - 8 ( 8 )

Abstract:


Background: Diabetes mellitus is a serious global health issue, currently affecting 425 million people and set to affect over 690 million people by 2045. It is a chronic disease characterized by hyperglycemia due to relative or absolute insulin hormone deficiency. Dipeptidyl peptidase-IV (DPP-IV) inhibitors are hypoglycemic agents augmenting the action of the incretin hormones that stimulate insulin secretion from the pancreatic beta cells.

Objectives: In this study synthesis and biological evaluation of seven piperazine derivatives 3a-g was carried out.

Methods: The synthesized molecules were characterized using proton-nuclear magnetic resonance, carbon- nuclear magnetic resonance, infrared spectroscopy and mass spectrometry.

Results: In vitro biological evaluation study showed comparable DPP-IV inhibitory activity for the targeted compounds ranging from 19%-30% at 100 µM concentration. Furthermore, the in vivo hypoglycemic activity of 3d was evaluated using streptozotocin-induced diabetic mice. It was found that compound 3d significantly decreased the blood glucose level when comparing the diabetic group treated with 3d to the control diabetic group. Quantum–Polarized Ligand Docking (QPLD) studies demonstrate that 3a-g fit the binding site of DPP-IV enzyme and form H-bonding with the backbones of R125, E205, E206, K554, W629, Y631, Y662, R669, and Y752.

Conclusion: Piperazine derivatives were found to be successful new scaffold as potential DPP-IV inhibitors.

Keywords:

Diabetes mellitus, dipeptidyl peptidase-IV inhibitors, piperazine, QPLD, streptozotocin, sulfonamide.

Affiliation:

Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman



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