Background: Benzimidazoles are important pharmacophores in drug discovery, and currently
its derivatives such as flubendazole, omeprazole, and astemizole are used for the treatment of
anthelmintic, ulcerative, and histaminic diseases, respectively.
Objectives: The aim of the current study was to investigate the antiglycation activity of nitrobenzimidazole
derivatives against fructose-mediated human serum albumin (HSA) glycation. The study
was also aimed at investigating the effects of newly identified antiglycation inhibitors on AGEsinduced
intracellular reactive oxygen species (ROS) production, and associated impaired proliferation
of the hepatocytes.
Methods: The present study focuses on the antiglycation activity of 6-nitrobenzimidazole derivatives
1-13 in in-vitro human serum albumin (HSA)- fructose model. These derivatives were also
identified as non-toxic against 3T3 mouse fibroblast cell-line in MTT-based assay. The effect of the
most promising derivative 5, 4-(6-nitro-1H-benzimidazol-2-yl)-1,2,3-benzenetriol, was studied in a
dose dependent manner, co-incubated with fructose-derived AGEs (0- 200 μg/mL) on rat hepatocytes
proliferation and associated intracellular generation of ROS via MTT-based assay and DCFHDA
Results: We found that derivative 5 ameliorates the elevated intracellular oxidative stress and associated
diminished proliferation of the hepatocytes in response to AGEs.
Conclusion: In conclusion, we identified novel 6-nitrobenzimidazole derivatives as antiglycation
agents through in-vitro, and cell-based models.