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 reduces the deterioration of gut-derived endogenous incretin hormones that are secreted in response to food ingestion
to stimulate the secretion of insulin from beta cells of pancreas.
Objective:
In this study, synthesis, characterization, and biological assessment of twelve novel phenanthridine
sulfonamide derivatives 3a-3l as potential DPP-IV inhibitors was carried out. The target compounds were docked to study
the molecular interactions and binding affinities against 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.
Molecular design, synthesis and in vitro biological evaluation of thienopyrimidine–hydroxamic acids as chimeric kinase HDAC inhibitors: a challenging approach to combat cancer
