Reema Abu Khalaf, Dalal Masalha, Dima Sabbah.

Current Computer-Aided Drug Design, 2019, 15, Ahead of Print. 

Abstract: Background: Lately, diabetes has become a main health concern for millions of people around the world. Objective: Dipeptidyl peptidase-IV (DPP-IV) enzyme inhibitors, gliptins, are a novel modality for treatment of type II diabetes by enhancing the activity of incretin hormones. Methods: Herein, quantum–polarized ligand docking and ligand-based pharmacophore modeling investigations were performed. Three novel 3,8-disubsituted-6-phenyl phenanthridine derivatives 3-5 have been designed, synthesized and characterized. Results: These compounds were proven to have DPP-IV inhibitory activity where compound 5 displayed the best activity with a % inhibition of 45.4 at 100 μM concentration. Conclusion: The computational results of this research shows that the size of the scaffold and the nature of the substitutions hinders the binding, suggesting future structural simplification.