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  • Title: Bioactivatable, membrane-permeant analogs of cyclic nucleotides as biological tools for growth control of C6 glioma cells.
    Author: Bartsch M, Zorn-Kruppa M, Kühl N, Genieser HG, Schwede F, Jastorff B.
    Journal: Biol Chem; 2003 Sep; 384(9):1321-6. PubMed ID: 14515995.
    Abstract:
    In the present study, the cAMP analogs 8-bromo-cAMP (8-Br-cAMP), N6-2'O-dibutyryl-cAMP (DBcAMP) and 8-para-chlorophenylthio-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, long-term 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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