Synthesis of 3-(substituted-benzylidene)-1, 3-dihydro-indolin derivatives and investigation of their roles against human protein kinase CK2

MEDI 110

Sureyya Olgen, olgen@pharmacy.ankara.edu.tr, Pharmaceutical Chemistry, University of Ankara, Faculty of Pharmacy, Tandogan, Ankara, 06100, Turkey, Claudia Götz, Medicinal Biochemistry and Molecular Biology, Saarland University, Homburg-Saarbrücken, D-66424, Germany, and Joachim Jose, joachim.jose@uni-duesseldorf.de, Bioanalytics, Institute for Pharmaceutical and Medicinal Chemistry, Heinrich-Heine University, Universitätsstr. 1, Düsseldorf, D-40225, Germany.
Protein kinases in general are thoroughly investigated drug targets and important targets for therapeutic intervention. Among the other members of the human kinome, protein kinase CK2 (casein kinase II) is a ubiquitous serine/threonine kinase that is typically found in tetrameric complexes consisting of two catalytic (alfa and/or alfa') and two regulatory beta subunits. Although there is growing evidence that beside the participation of CK2 in a complex series of cellular function it is also involved in cell viability, cell proliferation and neoplastic transformation. Despite the growing evidence on CK2 participation in malignant transformation and cancer, only few inhibitors of this enzyme are available at the moment. In the present study a series of 3-benzylidene-1, 3-dihydroindolin-2-thiones derivatives and the corresponding indolin-2-one congeners were synthesized and tested on inhibition of human recombinant protein kinase CK2 enzyme in vitro. It turned out, that 3-(4-chlorobenzylidene)-1, 3-dihydro-indol-2-thione is a an active inhibitor of human CK 2 with an IC50 value of 11,5 µM.

 

General Poster Session
7:00 PM-9:00 PM, Sunday, 10 September 2006 Moscone Center -- Hall D, Poster

Division of Medicinal Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006