title: Derivatives of 6-Nitrobenzimidazole Inhibit Fructose-Mediated Protein Glycation and Intracellular Reactive Oxygen Species Production.
abstract: 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.
  
  
  OBJECTIVE
  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 technique, respectively.
  
  
  RESULTS
  We found that derivative 5 ameliorates the elevated intracellular oxidative stress and associated diminished proliferation of the hepatocytes in response to AGEs.
  
  
  CONCLUSIONS
  In conclusion, we identified novel 6-nitrobenzimidazole derivatives as antiglycation agents through in-vitro, and cell-based models.
authors.affiliation: Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan.
authors.forename: Humera
authors.initials: H
authors.lastname: Jahan
authors.affiliation: Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan.
authors.forename: Muhammad I
authors.initials: MI
authors.lastname: Choudhary
authors.affiliation: Department of Chemistry, Bacha Khan University Charsadda, Khyber Pukhtoonkhwa, Pakistan.
authors.forename: Zarbad
authors.initials: Z
authors.lastname: Shah
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan.
authors.forename: Khalid M
authors.initials: KM
authors.lastname: Khan
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan.
authors.forename: Atta-Ur
authors.initials: AU
authors.lastname: Rahman
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001562:Benzimidazoles / Q000737:chemistry* / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D005632:Fructose / Q000378:metabolism*; D006031:Glycosylation / Q000187:drug effects; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects; D006801:Humans; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012709:Serum Albumin / Q000378:metabolism*
chemical_list: D001562:Benzimidazoles; D017382:Reactive Oxygen Species; D012709:Serum Albumin; D005632:Fructose; C038747:2-nitrobenzimidazole
keywords: 6-Nitrobenzimidazole derivatives; advanced glycation end products; fructose-derived AGEs; intracellular oxidative stress; protein glycation