Synthesis, kinase inhibitory potencies and in vitro antiproliferative activity of isoindigo and 7'-azaisoindigo derivatives substituted by Sonogashira cross-coupling.
In the course of structure-activity relationship studies we were interested in the synthesis of isoindigo and 7'-azaisoindigo derivatives substituted at the N-1 position by a 1-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl), at the 5'-position by various chains introduced by Sonogashira cross-coupling and substituted or not at the 5-position by a bromine atom. To get an insight into the substitution pattern required for the best biological potencies, their kinase inhibitory potencies and their in vitro antiproliferative activities were evaluated. The derivatives were tested toward four protein kinases (CDK5/p25, GSK3, CK1, Dyrk1A) and their in vitro antiproliferative activity was tested against two human myeloid leukaemia cell lines (K562 and HL60).
Bouchikhi
Fadoua
F
Université Blaise Pascal, SEESIB-UMR CNRS 6504, 24 Avenue des Landais, 63177 Aubière Cedex, France.
Anizon
Fabrice
F
Moreau
Pascale
P
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020014:K562 Cells; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D007211:Indoles; D047428:Protein Kinase Inhibitors; C529858:azaisoindigo; C049010:isoindigotin; D017346:Protein Serine-Threonine Kinases