ANALOGS OF 6-METHYL-9-BETA-D-RIBOFURANOSYLPURINE
ANALOGS OF 6-METHYL-9-BETA-D-RIBOFURANOSYLPURINE
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DOI：
10.1021/jm00307a010
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发表时间：
1968-01-01
影响因子：
7.3
通讯作者：
HEWSON, K
中科院分区：
文献类型：
--
作者：
MONTGOMERY, JA;HEWSON, K
G-Methyl-9-t3-D-ribofuranosylpurine, 9-(2-deoxy-| 3-n-ribofuranosyl)-G-methylpurine, 6-methyl-9-0-u-xylofuranosylpurine, 2-fluoro-6-methyl-9-/3-u-ribofuranosylpurine, and 6-ethyl-9-/3-D-ribofiiranosylpurine were prepared by fusion of the appropriate O-acetyl sugars and purines. The assignment, of the anomeric configuration to the nucleosides thus obtained was based on an analysis of their pmr spectra. Evidence is presented that the cytotoxicity of these nucleosides, determined using human epidermoid carcinoma cells no. 2 in culture, may correlate with the efficiency with which they are converted to nucleotides by adenosine kinase.The toxicity2 and antitumor activity2 of 6-methylpurine caused Gordon, et al., 4 56to synthesize its ribonucle-oside, a compound that is more than 200-fold as cytotoxic to HEp-2 cells as 6-methylpurine itself.” In addition, a HEp-2 cell line that has lost AMP pyrophosphoryl-use and is resistant to 2-fluoroadenine (HEp-2/l’A) and cross-resistant to 6-methylpurine is sensitive to 6-methylpurinc ribonucleoside.” This activity can be. explained by the fact that the ribonucleoside is an excellent substrate for adenosine kinase” and there-fore can be converted to its cytotoxic form, the ribonucleotide, in cells lacking the pyrophosphorylase that normally converts thepurine base to its ribonucleotide.
