Zhen W, Jayaram H N, Marquez V E, Goldstein B M, Cooney D A, Weber G
Laboratory for Experimental Oncology, Indiana University School of Medicine, Indianapolis 46202-5200.
Biochem Biophys Res Commun. 1991 Oct 31;180(2):933-8. doi: 10.1016/s0006-291x(05)81155-6.
2-beta-D-Arabinofuranosylthiazole-4-carboxamide and 2-beta-D-xylofuranosyl-thiazole-4-carboxamide are sugar modified analogues of tiazofurin, a C-glycosyl nucleoside which after anabolism to the dinucleotide, TAD (thiazole-4-carboxamide adenine dinucleotide), exhibits antitumor activity. However, ara-T and xylo-T did not exhibit cytotoxicity. Compared to tiazofurin, only 12.5% of the ara-T and 8.8% of the xylo-T were metabolized to TAD derivatives by human myelogenous leukemia K562 cells. This was reflected in the finding that guanylate pools were not depressed after treatment with either tiazofurin derivative. These results provide evidence that the ribose moiety is essential for the metabolism and cytotoxicity of tiazofurin. This investigation should be helpful in the design of new analogues of tiazofurin for future clinical trials.
2-β-D-阿拉伯呋喃糖基噻唑-4-甲酰胺和2-β-D-木糖呋喃糖基噻唑-4-甲酰胺是噻唑呋林的糖修饰类似物，噻唑呋林是一种C-糖基核苷，在合成代谢为二核苷酸TAD（噻唑-4-甲酰胺腺嘌呤二核苷酸）后具有抗肿瘤活性。然而，ara-T和xylo-T没有表现出细胞毒性。与噻唑呋林相比，人髓性白血病K562细胞仅将12.5%的ara-T和8.8%的xylo-T代谢为TAD衍生物。这一发现反映在用任何一种噻唑呋林衍生物处理后，鸟苷酸池并未降低。这些结果证明核糖部分对于噻唑呋林的代谢和细胞毒性至关重要。这项研究应有助于设计新的噻唑呋林类似物用于未来的临床试验。
