title: Polyhalogenobenzimidazoles: synthesis and their inhibitory activity against casein kinases.
abstract: A series of novel polyhalogenated benzimidazoles have been prepared by exhaustive bromination of a variety of 2-substituted benzimidazoles. The efficacy of both new compounds and a number of their previously described cognates as inhibitors of casein kinases CK1, CK2 and G-CK was investigated. The type of N-1 alkyl substituent as well as introduction of a polyfluoroalkyl moiety at position 2 did not markedly influence the inhibitory efficacy toward CK2 of the respective 4,5,6,7-tetrabromobenzimidazole derivatives which conversely were almost ineffective toward CK1 and G-CK. However, 4,5,6,7-tetrabromobenzimidazoles substituted at position 2 with either chlorine, bromine or sulfur atom, while manifesting a still considerable inhibitory activity against CK2 (IC(50) in the 0.49-0.93 microM range) proved to be potentially powerful inhibitors also against CK1 (IC(50) in the 18.4-2.2 microM range).
authors.affiliation: Institute of Chemistry, Agricultural University, 159C Nowoursynowska St., 02-787 Warsaw, Poland.
authors.forename: Mariola
authors.initials: M
authors.lastname: Andrzejewska
authors.forename: Mario A
authors.initials: MA
authors.lastname: Pagano
authors.forename: Flavio
authors.initials: F
authors.lastname: Meggio
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Brunati
authors.forename: Zygmunt
authors.initials: Z
authors.lastname: Kazimierczuk
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D047390:Casein Kinase II; D047388:Casein Kinases; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006219:Halogens / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D008099:Liver / Q000201:enzymology; D008321:Mammary Glands, Animal / Q000201:enzymology; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D006219:Halogens; D047428:Protein Kinase Inhibitors; D000255:Adenosine Triphosphate; D011494:Protein Kinases; D047390:Casein Kinase II; D047388:Casein Kinases; D017346:Protein Serine-Threonine Kinases