Synthesis and antiproliferative activity of 7-azaindirubin-3'-oxime, a 7-aza isostere of the natural indirubin pharmacophore.

Abstract

The bis-indole alkaloid indirubin and its analogues bear a very interesting natural pharmacophore. They are recognized mainly as kinase inhibitors, but several other activities make them possible candidates for preclinical studies. Based on the previously reported activity of 7-bromoindirubin-3'-oxime and its derivatives, the synthesis of indirubins bearing a heterocyclic nitrogen atom at position 7 was carried out. Herein, we report the first synthesis of 7-azaindirubin-3'-oxime (12) as well as its antiproliferative activity against 57 cancer cell lines and its inhibitory activity against a series of kinases. 7-Azaindirubin (10) and its 3'-oxime derivative (12) showed reduced activity as kinase inhibitors in comparison with other known indirubin derivatives, but antiproliferative activity with a best GI(50) value of 0.77 microM.

• Authors: Marina Kritsanida, Prokopios Magiatis, Alexios-Leandros Skaltsounis, Youyi Peng, Peng Li, Lawrence P Wennogle
• Journal: Journal of natural products (J Nat Prod) Vol. 72 Issue 12 Pg. 2199-202 (Dec 2009) ISSN: 1520-6025 [Electronic] United States
• PMID: 19994845 (Publication Type: Journal Article)

Chemical References

• 7-azaindirubin-3'-oxime
• Antineoplastic Agents
• Cyclin-Dependent Kinase Inhibitor Proteins
• Indole Alkaloids
• Indoles
• indirubin

Topics

• Amino Acid Sequence
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cyclin-Dependent Kinase Inhibitor Proteins (chemical synthesis, chemistry, pharmacology)
• Drug Screening Assays, Antitumor
• Female
• Humans
• Indole Alkaloids (chemical synthesis, chemistry, pharmacology)
• Indoles (pharmacology)
• Molecular Structure