Title:Phenanthridine Sulfonamide Derivatives as Potential DPP-IV Inhibitors:
Design, Synthesis and Biological Evaluation
Volume: 18
Issue: 1
Author(s): Reema Abu Khalaf*, Shorooq Alqazaqi, Maram Aburezeq, Dima Sabbah, Ghadeer Albadawi and Ghassan Abu Sheikha
Affiliation:
- Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman,Jordan
Keywords:
Diabetes, dipeptidyl peptidase-IV, inhibitors, phenanthridine, sulfonamide, QPLD.
Abstract: Background: Diabetes mellitus is a chronic metabolic disorder, characterized by hyperglycemia
over a prolonged period, disturbance of fat, protein, and carbohydrate metabolism, resulting
from defective insulin secretion, insulin action or both. Dipeptidyl peptidase-IV (DPP-IV) inhibitors
are relatively a new class of oral hypoglycemic agents that reduce the deterioration of gutderived
endogenous incretin hormones secreted in response to food ingestion to stimulate the secretion
of insulin from beta cells of the pancreas.
Objective: In this study, synthesis, characterization, and biological assessment of twelve novel phenanthridine
sulfonamide derivatives 3a-3l as potential DPP-IV inhibitors were carried out. The target
compounds were docked to study the molecular interactions and binding affinities against the
DPP-IV enzyme.
Methods: The synthesized molecules were characterized using 1H-NMR, 13C-NMR, IR, and MS.
Quantum-polarized ligand docking (QPLD) was also performed.
Results: In vitro biological evaluation of compounds 3a-3l reveals comparable DPP-IV inhibitory
activities ranging from 10%-46% at 100 μM concentration, where compound 3d harboring ortho-
fluoro moiety exhibited the highest inhibitory activity. QPLD study shows that compounds
3a-3l accommodate DPP-IV binding site and form H-bonding with the R125, E205, E206, S209,
F357, R358, K554, W629, S630, Y631, Y662, R669, and Y752 backbones
Conclusion: In conclusion, phenanthridine sulfonamides could serve as potential DPP-IV inhibitors
that require further structural optimization in order to enhance their inhibitory activity.