Novel hexahydropyridoindole derivative as prospective agent against oxidative damage in pancreatic β cells
|Published in||Medicinal Chemistry. 2011, vol. 7, no. 6, p. 711-7|
|Abstract||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.|
|Keywords||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|
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|Research group||Mitochondries et sécrétion d'insuline (671)|
|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. 711-7. doi: 10.2174/157340611797928370 https://archive-ouverte.unige.ch/unige:25508|