Scientific article

Novel hexahydropyridoindole derivative as prospective agent against oxidative damage in pancreatic β cells

Published inMedicinal chemistry, vol. 7, no. 6, p. 711-717
Publication date2011

The potential protective effect of (±)-8-methoxy-1,3,4,4a,5,9b-hexahydro-pyrido[4,3-b]indole-2-carboxylic acid ethyl ester (II) was assessed against hydrogen peroxide (H2O2)-cytotoxicity in rat pancreatic INS-1E β cells and compared with the effect of the related pyridoindole, stobadine (I), a promising indole-type reference antioxidant. Only pre-treatment with the compound (II) led to a significant preservation of the metabolic and secretory functions of the cells exposed to H2O2. The caspase-9 and -3 activities, as well as the early apoptotic changes of plasma membrane, were suppressed in the cells pre-incubated with both of compounds tested. However, only pyridoindole (II) inhibited profoundly the time-delayed apoptotic changes, These results suggest that pyridoindole (II) characterized by enhanced intrinsic antioxidant efficiency, may protect β cells against cytotoxic effects of H2O2, involved in the development of both type 1 and type 2 diabetes.

  • Animals
  • Antioxidants/chemical synthesis/chemistry/pharmacology
  • Apoptosis/drug effects
  • Caspases/antagonists & inhibitors/metabolism
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Enzyme Inhibitors/chemical synthesis/chemistry/pharmacology
  • Hydrogen Peroxide/antagonists & inhibitors/pharmacology
  • Indoles/chemical synthesis/chemistry/pharmacology
  • Insulin-Secreting Cells/cytology/drug effects/metabolism
  • Molecular Structure
  • Oxidative Stress/drug effects
  • Rats
  • Structure-Activity Relationship
Citation (ISO format)
RAČKOVÁ, Lucia et al. Novel hexahydropyridoindole derivative as prospective agent against oxidative damage in pancreatic β cells. In: Medicinal chemistry, 2011, vol. 7, n° 6, p. 711–717. doi: 10.2174/157340611797928370
ISSN of the journal1573-4064

Technical informations

Creation10/31/2012 1:04:00 PM
First validation10/31/2012 1:04:00 PM
Update time03/14/2023 7:57:02 PM
Status update03/14/2023 7:57:02 PM
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