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 TI (also known as casein kinases I and II), were found to be effective inhibitors of Saccharomyces cerevisiae CK IT, 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. Ah inhibitors are competitive with respect to ATP (and GTP with CK II), the two latter with K-i values in the range 0.2 - 0.6 mu M for CK II from yeast and mammalian sources. (C) 1995 Academic Press, Inc.