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

Publié dansMedicinal chemistry, vol. 7, no. 6, p. 711-717
Date de publication2011
Résumé

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.

Mots-clés
  • 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 (format ISO)
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
Identifiants
ISSN du journal1573-4064
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Création31/10/2012 13:04:00
Première validation31/10/2012 13:04:00
Heure de mise à jour14/03/2023 19:57:02
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