Anthranilic Acid Derivatives: Novel Inhibitors of Protein Glycation and the Associated Oxidative Stress in the Hepatocytes

摘要

Background: Anthranilic acid derivatives are important pharmacophores in drug discovery.Several of them are currently being used, such as mefenamic acid and meclofenamates,possess analgesic, anti-inflammatory and antipyretic activities. Some anthranilic acid-based scaffoldshave also been reported for the management of metabolic disorders.Objectives: The aim of the current study was to investigate the antiglycation potential of 2-anilinobenzoic acid derivatives against (N-phenylanthranilic acid) fructose- human serum albumin (HSA)glycation. The study also analyzed the effects of newly identified antiglycation inhibitors onAGEs-mediated intracellular reactive oxygen species production, and associated impaired proliferationof the hepatocytes.Methods: The present study focuses on the antiglycation activity of 2- anilinobenzoic acid derivatives1-18 in in-vitro human serum albumin (HSA)- fructose model. These derivatives were alsoidentified as non-toxic to 3T3 mouse fibroblast cell-line using metabolic assay. The effect of themost promising derivative 1, 2- (2, 4- dinitroanilino)benzoic acid, was studied in a dose dependentmanner, co-incubated with fructose-derived AGEs (0- 200 μg/mL), on rat hepatocytes proliferationand associated intracellular generation of ROS via MTT assay and DCFH-DA technique, respectively.Results: We found that derivative 1 ameliorates the elevated intracellular oxidative stress and associateddiminished proliferation of the hepatocytes in response to AGEs.Conclusion: In conclusion, we identify novel 2- anilino benzoic acid derivatives as antiglycationagents through in-vitro and cellular-based models.