title: 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.affiliation: Department of Pharmacognosy and Natural Products Chemistry, University of Athens, Panepistimiopolis Zografou, 15771, Athens, Greece.
authors.forename: Marina
authors.initials: M
authors.lastname: Kritsanida
authors.forename: Prokopios
authors.initials: P
authors.lastname: Magiatis
authors.forename: Alexios-Leandros
authors.initials: AL
authors.lastname: Skaltsounis
authors.forename: Youyi
authors.initials: Y
authors.lastname: Peng
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Lawrence P
authors.initials: LP
authors.lastname: Wennogle
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D026121:Indole Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D015394:Molecular Structure
chemical_list: C546302:7-azaindirubin-3'-oxime; D000970:Antineoplastic Agents; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D026121:Indole Alkaloids; D007211:Indoles; C027185:indirubin