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Publication Date:
June 2005
ISSN:
1437-4315
DOI:
10.1515/BC.2003.148

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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Ludwig, Stephan / Sies, Helmut / Stoffel, Markus / Turk, Boris / Wittinghofer, Alfred / Baumeister, Wolfgang / Bergeron, John / Bogyo, Matthew / Bürkle, Alexander / Cadenas, Enrique / Chiti, Fabrizio / Dikic, Ivan / Dobson, Christopher / Driessen, Arnold / Fritz, Hans / Gevaert, Kris / Hammann, Christian / Hartl, F. Ulrich / Häussinger, Dieter / Hiscott, John / Igarashi, Yasuyuki / Klotz, Lars-Oliver / Krüger, Achim / Magdolen, Viktor / Müschen, Markus / Narumiya, Shuh / Naumann, Michael / Pejler, Gunnar / Pfanner, Nikolaus / Pike, Robert / Potempa, Jan / Saftig, Paul / Sandhoff, Konrad / Schaffner, Walter / Sinning, Irmgard / Sommerhoff, Christian P.

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Bioactivatable, Membrane-Permeant Analogs of Cyclic Nucleotides as Biological Tools for Growth Control of C6 Glioma Cells

M. Bartsch / M. Zorn-Kruppa / N. Kühl / H.-G. Genieser / F. Schwede / B. Jastorff

Citation Information: Biological Chemistry. Volume 384, Issue 9, Pages 1321–1326, ISSN (Print) 1431-6730, DOI: 10.1515/BC.2003.148, June 2005

Publication History:
Published Online:
2005-06-01

Abstract

In the present study, the cAMP analogs 8-bromocAMP (8-Brc-AMP), N6-2'O-dibutyryl-cAMP (DBcAMP) and 8-parachlorophenylthio-cAMP (8-CPT-cAMP), as well as the corresponding cAMP-acetoxymethyl (AM)-ester-prodrugs were tested in a HPLC study for their membrane permeability, intracellular accumulation and biotransformation. Antiproliferative activities of these compounds were studied in the rat C6 glioma cell line. Chromatographic analysis revealed that the AM-ester analogs of the cyclic nucleotides penetrate quantitatively into rat C6 glioma cells and generate high amounts of their parent cyclic nucleotides intracellularly within 60 min; however, longterm growth inhibition tested in C6 cells is only slightly enhanced with the AM-ester prodrugs of 8-Br-cAMP or DBcAMP.

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