Τίτλος:
Synthesis and antiproliferative activity of 7-azaindirubin-3′-oxime, a 7-aza isostere of the natural indirubin pharmacophore
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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-3́-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-3́-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 3́-oxime derivative (12) showed reduced activity as kinase inhibitors in comparison with other known indirubin derivatives, but antiproliferative activity with a best GI50 value of 0.77 μM. © 2009 American Chemical Society and American Society of Pharmacognosy.
Συγγραφείς:
Kritsanida, M.
Magiatis, P.
Skaltsounis, A.-L.
Peng, Y.
Li, P.
Wennogle, L.P.
Περιοδικό:
Tropical Journal of Natural Product Research
Λέξεις-κλειδιά:
2,3 dibromo 3h pyrrole [2,3 b]pyridine; 3' oxime derivative; 5 bromo 7,7' diaza 1,1' dimethylisoindigo; 7 aza 1 methylindirubin; 7 aza 1 methylindirubin 3' oxime; 7 azaindirubin; 7 azaindirubin 3' oxime; 7 azaisatin; 7,7' diaza 1,1' dimethylisoindigo; indirubin; indole derivative; oxime derivative; phosphotransferase inhibitor; unclassified drug, article; cancer cell culture; drug activity; inhibition kinetics; pharmacophore; synthesis, Amino Acid Sequence; Antineoplastic Agents; Cyclin-Dependent Kinase Inhibitor Proteins; Drug Screening Assays, Antitumor; Female; Humans; Indole Alkaloids; Indoles; Molecular Structure
