New inhibitors of protein kinase CK2, analogues of benzimidazole and benzotriazole.
Derivatives of 4,5,6,7-tetrabromobenzotriazole (TBBt) and 4,5,6,7-tetrabromobenzimidazole (TBBi) with IC50 in the low micromolar range and with high selectivity belong to the most promising inhibitors of protein kinase CK2 (casein kinase 2). Treatment of various cell lines with TBBt, TBBi or 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole (DMAT) affected cell viability with simultaneous induction of apoptosis. The inhibitory activity of newly synthesized hydroxyalkyl derivatives of TBBi and TBBt depends on the length of the alkyl chain. The hydroxypropyl substituted derivatives show higher or similar inhibitory activity than the parent compounds when tested with human protein kinase CK2. To test the distribution of this class of compounds in mammals, [14C] TBBi was synthesized.
Institute of Biochemistry and Biophysics, Pawińskiego 5a, 02-106, Warsaw, Poland. majka@ibb.waw.pl
Maria
M
Bretner
Andzelika
A
Najda-Bernatowicz
Maja
M
Łebska
Grazyna
G
Muszyńska
Anna
A
Kilanowicz
Andrzej
A
Sapota
D001562:Benzimidazoles / Q000737:chemistry*; D047390:Casein Kinase II / Q000037:antagonists & inhibitors*; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology*; D014230:Triazoles / Q000032:analysis / Q000737:chemistry* / Q000494:pharmacology
C405354:4,5,6,7-tetrabromobenzotriazole; D001562:Benzimidazoles; D047428:Protein Kinase Inhibitors; D014230:Triazoles; C012771:benzotriazole; C031000:benzimidazole; D047390:Casein Kinase II