Journal of Clinical & Experimental Pharmacology

Design, Synthesis and biological Evaluation of Benzamide derivatives for Glucokinase Activation

17^th International Conference on PHARMACOLOGY AND DRUG DISCOVERY

June 15-16, 2023 | Rome, Italy

Abdulaseem Kazi

SNJB�??s Shriman Sureshdada Jain College of Pharmacy, India

Scientific Tracks Abstracts: J Clin Exp Pharmacol

Abstract:

Glucokinase (GK) is a cytoplasmic enzyme that metabolizes glucose to glucose-6-phosphate and supports adjusting blood glucose level within the normal range in humans. In pancreatic β-cells, it plays a leading role in governing the glucose stimulated secretion of insulin, and in liver hepatocyte cells, it controls the metabolism of carbohydrates. GK acts as a promising drug target for treating patients with type-2 diabetes mellitus (T2DM). In the present work we have designed and developed several benzamide derivatives as GK activators for the treatment of T2DM. All of the compounds were docked on human GK enzyme (PDB ID 1V4S), and the results were compared to the native ligand present in enzyme. In addition, ADMET analysis and drug-likeness characteristics calculations were used to test all of the developed compounds. Many of the designed derivatives have a lower binding free energy (ranging from -7.4 to -10.3 kcal/mol) than the native ligand present in the enzyme structure. The most potent molecules were chosen for wet lab synthesis, and their characterization is done by FTIR, 1H & 13C NMR, and Mass spectroscopy. All synthesized derivatives were tested for in vitro GK assay and evaluated for their glucose-lowering properties in the experimental animals. Compounds 5l and A16, which are the most potent among the screened molecules, showed activation rates of 113.45±0.98% and 118.78±1.08 percent, respectively, among the synthesized molecules. The in vivo antidiabetic efficacy of all synthesized compounds was tested in a STZ-induced diabetic model in rats. Different serum biochemical markers were estimated to assess the antidiabetic potential. When compared to the metformin-treated group, compound 5l and A16 showed considerable antidiabetic potential among all the compounds. It was determined that compound 5l and A16 may be used as a lead molecule for the development of new anti-diabetic drugs.

Biography :

Kazi Abdulaseem Abdulhaiee is professor at SNJB’s Shriman Sureshdada Jain College of Pharmacy, Maharashtra, India.