核苷缀合物。7. 醚脂的1-β-D-阿拉伯呋喃糖基胞嘧啶缀合物的合成及抗肿瘤活性。
Nucleoside conjugates. 7. Synthesis and antitumor activity of 1-beta-D-arabinofuranosylcytosine conjugates of ether lipids.
作者信息
Hong C I, An S H, Buchheit D J, Nechaev A, Kirisits A J, West C R, Berdel W E
出版信息
J Med Chem. 1986 Oct;29(10):2038-44. doi: 10.1021/jm00160a041.
Three new 1-beta-D-arabinofuranosylcytosine conjugates of ether lipids (alkyl glycerols) linked by a pyrophosphate diester bond have been prepared and evaluated against mouse leukemia L1210 and P388. These include ara-CDP-rac-1-O-hexadecyl-2-O-palmitoylglycerol (9a) (ara-CDP = 1-beta-D-arabinofuranosylcytosine 5'-diphosphate), ara-CDP-rac-1-O-octadecyl-2-O-palmitoylglycerol (9b), and ara-CDP-rac-1-O-octadecyl-2-O-methylglycerol (9c). Among them, conjugate 9a produced significant increase in life span (200-293%) in mice bearing ip and ic implanted L1210 lymphoic leukemia at a total dose of 400-500 mg (406-508 mumol/kg). Significant schedule dependence was not observed when the conjugate was given ip once daily on day 1, days 1, 5, and 9, and days 1-5. The new conjugates are water soluble by sonication.
已经制备了三种通过焦磷酸二酯键连接的醚脂（烷基甘油）的新型1-β-D-阿拉伯呋喃糖基胞嘧啶共轭物，并针对小鼠白血病L1210和P388进行了评估。这些包括阿糖胞苷二磷酸-外消旋-1-O-十六烷基-2-O-棕榈酰甘油（9a）（阿糖胞苷二磷酸=1-β-D-阿拉伯呋喃糖基胞嘧啶5'-二磷酸）、阿糖胞苷二磷酸-外消旋-1-O-十八烷基-2-O-棕榈酰甘油（9b）和阿糖胞苷二磷酸-外消旋-1-O-十八烷基-2-O-甲基甘油（9c）。其中，共轭物9a在总剂量为400-500mg（406-508μmol/kg）时，使腹腔注射和脑内植入L1210淋巴细胞白血病的小鼠的寿命显著延长（200-293%）。当共轭物在第1天、第1、5和9天以及第1-5天每天腹腔注射一次时，未观察到明显的给药方案依赖性。这些新型共轭物通过超声处理可溶于水。
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