Design, Synthesis and Antidiabetic Activity of Novel Sulfamoyl Benzamide Derivatives as Glucokinase Activators
Open Access
- 2 November 2018
- journal article
- Published by Chitkara University Publications in Journal of Pharmaceutical Technology, Research and Management
- Vol. 6 (2), 115-124
- https://doi.org/10.15415/jptrm.2018.62008
Abstract
The present work has been planned to design, synthesize and evaluate the antidiabetic potential of a series of sulfamoyl benzamide derivatives as potential glucokinase (GK) activators. A new series of sulfamoyl benzamide derivatives was synthesized starting from 3-nitrobenzoic acid and characterized. In silico docking studies were performed to determine the binding interactions for the best fit conformations in the allosteric site of GK enzyme. Based on the results of in silico studies, the selected molecules were tested for their antidiabetic activity in animal studies (alloxan induced diabetic animal model). Compound 7 exhibited highest antidiabetic activity in animal studies. The results of in vivo antidiabetic activity studies were found to be in parallel to that of docking studies. These newly synthesized sulfamoyl benzamide derivatives thus can be treated as the initial hits for the development of novel, safe, effective and orally bioavailable GK activators as therapeutic agents for the treatment of type 2 diabetes.Keywords
This publication has 41 references indexed in Scilit:
- Discovery of novel dual-action antidiabetic agents that inhibit glycogen phosphorylase and activate glucokinaseEuropean Journal of Medicinal Chemistry, 2012
- Type 2 Diabetes Mellitus: A Review of Current TrendsOman Medical Journal, 2012
- Discovery of (S)-6-(3-Cyclopentyl-2-(4-(trifluoromethyl)-1H-imidazol-1-yl)propanamido)nicotinic Acid as a Hepatoselective Glucokinase Activator Clinical Candidate for Treating Type 2 Diabetes MellitusJournal of Medicinal Chemistry, 2012
- Design, synthesis and biological evaluation of novel glucokinase activatorsChinese Chemical Letters, 2011
- 2,3-Disubstituted acrylamides as potent glucokinase activatorsBioorganic & Medicinal Chemistry Letters, 2010
- Glucokinase activators (GKAs) promise a new pharmacotherapy for diabeticsF1000 Medicine Reports, 2010
- Frog2: Efficient 3D conformation ensemble generator for small compoundsNucleic Acids Research, 2010
- Discovery of novel 2-(pyridine-2-yl)-1H-benzimidazole derivatives as potent glucokinase activatorsBioorganic & Medicinal Chemistry Letters, 2009
- AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibilityJournal of Computational Chemistry, 2009
- Diabetes-Related Microvascular and Macrovascular Diseases in the Physical Therapy SettingPTJ: Physical Therapy & Rehabilitation Journal, 2008