Bioactivatable, membrane-permeant analogs of cyclic nucleotides as biological tools for growth control of C6 glioma cells.
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.
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D001711:Biotransformation; D003994:Bucladesine / Q000493:pharmacokinetics / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D000242:Cyclic AMP / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D005910:Glioma / Q000473:pathology*; D009712:Nucleotides, Cyclic / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011355:Prodrugs / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D013873:Thionucleotides / Q000493:pharmacokinetics / Q000494:pharmacology
D009712:Nucleotides, Cyclic; D011355:Prodrugs; D013873:Thionucleotides; D015124:8-Bromo Cyclic Adenosine Monophosphate; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D003994:Bucladesine; D000242:Cyclic AMP