Bioactivatable, membrane-permeant analogs of cyclic nucleotides as biological tools for growth control of C6 glioma cells

被引：28

作者：

Bartsch, M

Zorn-Kruppa, M

Kühl, N

Genieser, HG

Schwede, F

Jastorff, B

机构：

[1] Univ Bremen, Zentrum Umweltforsch & Umwelttechnol, Abt Bioorgan Chem, D-28359 Bremen, Germany

[2] BIOLOG, Inst Life Sci, D-28071 Bremen, Germany

来源：

BIOLOGICAL CHEMISTRY | 2003年 / 384卷 / 09期

关键词：

biotransformation; cAMP analogs; cAMP AM-prodrugs; growth inhibition; intracellular concentration of second messenger analogs; membrane permeation;

D O I：

10.1515/BC.2003.148

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In the present study, the cAMP analogs 8-bromocAMP (8-BrcAMP), N6-2OdibutyrylcAMP (DBcAMP) and 8-parachlorophenylthiocAMP (8-CPTcAMP), as well as the corresponding cAMPacetoxymethyl (AM)esterprodrugs 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 AMester 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 AMester prodrugs of 8-BrcAMP or DBcAMP.

引用

页码：1321 / 1326

页数：6

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