Halogenated benzimidazoles and benzotriazoles as selective inhibitors of protein kinases CK I and CK II from Saccharomyces cerevisiae and other sources.
Several halogeno benzimidazole riboside inhibitors of animal and plant protein kinases CK I and CK II (also known as casein kinases I and II), were found to be effective inhibitors of Saccharomyces cerevisiae CK II, but not of the 27-kDa CK.I or the 45-kDa CK I. The previously reported 5,6-dichloro-2-azabenzimidazole, which preferentially inhibits plant CK II relative to CK I, discriminates even more effectively between the yeast CK I and CK II enzymes. Two new analogues, tetrahalogeno-2-azabenzimidazoles, are even more potent inhibitors of CK II and much less so of CK I from yeast and animal sources. All inhibitors are competitive with respect to ATP (and GTP with CK II), the two latter with Ki values in the range 0.2-0.6 microM for CK II from yeast and mammalian sources.
Szyszka
R
R
Department of Molecular Biology, Maria Curie-Skłodowska University, Lublin, Poland.
Grankowski
N
N
Felczak
K
K
Shugar
D
D
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D002287:Carcinoma, Krebs 2 / Q000201:enzymology*; D047390:Casein Kinase II; D047388:Casein Kinases; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D051379:Mice; D010944:Plants / Q000201:enzymology; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000494:pharmacology*
D001562:Benzimidazoles; D047428:Protein Kinase Inhibitors; D014230:Triazoles; D047390:Casein Kinase II; D047388:Casein Kinases; D017346:Protein Serine-Threonine Kinases