title: Design, Synthesis and Biological Evaluation of N4-Sulfonamido-Succinamic, Phthalamic, Acrylic and Benzoyl Acetic Acid Derivatives as Potential DPP IV Inhibitors.
abstract: As incidence rate of type II diabetes mellitus continues to rise, there is a growing need to identify novel therapeutic agents with improved efficacy and reduced side effects. Dipeptidyl peptidase IV (DPP IV) is a multifunctional protein involved in many physiological processes. It deactivates the natural hypoglycemic incretin hormone effect. Inhibition of this enzyme increases endogenous incretin level, incretin activity and should restore glucose homeostasis in type II diabetic patients making it an attractive target for the development of new antidiabetic drugs. One of the interesting reported anti- DPP IV hits is Gemifloxacin which is used as a lead compound for the development of new DPP IV inhibitors. In the current work, design and synthesis of a series of N4-sulfonamido-succinamic, phthalamic, acrylic and benzoyl acetic acid derivatives was carried out. The synthesized compounds were evaluated for their in vitro anti-DPP IV activity. Some of them have shown reasonable bioactivity, where the most active one 17 was found to have an IC50 of 33.5 μM.
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Jordan;
authors.forename: Reema Abu
authors.initials: RA
authors.lastname: Khalaf
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Jordan;
authors.forename: Ghassan Abu
authors.initials: GA
authors.lastname: Sheikha
authors.affiliation: Faculty of Pharmacy, Zarqa University, Zarqa, Jordan;
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Al-Sha'er
authors.affiliation: Drug Discovery Unit, Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Jordan, Amman, Jordan.
authors.forename: Mutasem
authors.initials: M
authors.lastname: Taha
keywords: Acrylic acid; DPP IV inhibitors; docking; pharmacophore modeling; phthalamic acid; succinamic acid; type II diabetes.