Synthesis, Structural Characterization and Docking Studies of Sulfamoyl- Phenyl Acid Esters as Dipeptidyl Peptidase-IV Inhibitors

Title:Synthesis, Structural Characterization and Docking Studies of Sulfamoyl- Phenyl Acid Esters as Dipeptidyl Peptidase-IV Inhibitors

Volume: 14 Issue: 2

Author(s): Reema Abu Khalaf*, Dima Sabbah, Eveen Al-Shalabi, Iyad Al-Sheikh, Ghadeer Albadawi and Ghassan Abu Sheikha

Affiliation:

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

Keywords: Acrylic acid, diabetes mellitus, DPP-IV inhibitors, glide docking, phthalamic acid, sulfamoyl acid ester.

Abstract: Background: Diabetes mellitus is a major worldwide health concern that has several serious complications including retinopathy, neuropathy, nephropathy and macrovascular diseases.

Objective: Dipeptidyl peptidase-IV (DPP-IV) inhibitors, gliptins, are a new class of antidiabetic agents that potentiate the action of incretins in decreasing the blood glucose levels.

Methods: In the present study, synthesis and characterization of a series of ten N4-sulfonamido-acrylic and phthalamic acid methyl esters (3a-e and 5a-e) were achieved.

Results: In vitro anti-DPP-IV activity of the synthesized compounds was evaluated, where compound 3b demonstrated the best activity with a % inhibition of 41.7 at 10 µM concentration and an IC50 of 23.9 µM. Moreover, Glide docking experiments revealed that our targeted compounds accommodate the binding site of DPP-IV and tend to form H-bonding with the backbones of R125, E206, S209, D545, K554, W629, Y631, and G632.

Conclusion: Modeling findings recommend the attachment of bulky hydrophobic group on the ester side of the structure in addition to harboring extra aromatic rings that might be beneficial for better binding interaction and biological activity.

Cite this article as:

Khalaf Abu Reema *, Sabbah Dima , Al-Shalabi Eveen , Al-Sheikh Iyad , Albadawi Ghadeer and Abu Sheikha Ghassan , Synthesis, Structural Characterization and Docking Studies of Sulfamoyl- Phenyl Acid Esters as Dipeptidyl Peptidase-IV Inhibitors, Current Computer-Aided Drug Design 2018; 14 (2) . https://dx.doi.org/10.2174/1573409914666180308164013