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Article Dans Une Revue Bioorganic and Medicinal Chemistry Année : 2009

Synthesis and kinase inhibitory activity of novel substituted indigoids.

Anne Beauchard
  • Fonction : Auteur
Hélène Laborie
  • Fonction : Auteur
Hervé Rouillard
  • Fonction : Auteur
  • PersonId : 761698
  • IdRef : 168736233
Olivier Lozach
Rémy Le Guével
  • Fonction : Auteur
  • PersonId : 835989
Thierry Besson
Valérie Thiéry

Résumé

The bis-indole indigoids are a promising protein kinase inhibitor scaffold to be further evaluated against the numerous human diseases that imply abnormal regulation of kinases including neurodegenerative disorders. In an effort to identify new pharmacological inhibitors of disease-relevant protein kinases with increased potency and selectivity, we designed, synthesized new 5,7-disubstituted or 6-substituted bis-indole derivatives. On the basis of our previous synthetic work, 22 selected compounds were tested on CDK1/cyclin B, CDK5/p25, DYRK1A, CK1, and GSK-3alpha/beta kinases, five kinases involved in Alzheimer's disease. Some of them were also evaluated for their cytotoxic and antiproliferative activities. 6-Nitro-3'-N-oxime-indirubin and 5-amino-3'-N-oxime-indirubin derivatives exhibited inhibitory activity in a submicromolar range against CDK1/cyclin B (0.18 and 0.1 microM, respectively), CK1 (0.6 microM and 0.13 microM) and GSK3 (0.04 microM and 0.36 microM).

Dates et versions

hal-00416031 , version 1 (11-09-2009)

Identifiants

Citer

Anne Beauchard, Hélène Laborie, Hervé Rouillard, Olivier Lozach, Yoan Ferandin, et al.. Synthesis and kinase inhibitory activity of novel substituted indigoids.. Bioorganic and Medicinal Chemistry, 2009, 17 (17), pp.6257-63. ⟨10.1016/j.bmc.2009.07.051⟩. ⟨hal-00416031⟩
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