Nucleosides and nucleotides .152. 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)uracil as a broad spectrum antitumor nucleoside
Nucleosides and nucleotides .152. 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)uracil as a broad spectrum antitumor nucleoside
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DOI：
10.1016/0960-894x(96)00339-3
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发表时间：
1996-08-20
影响因子：
2.7
通讯作者：
Sasaki, T
中科院分区：
文献类型：
--
作者：
Matsuda, A;Hattori, H;Sasaki, T
1-（3-C-Ethynyl-beta-D-ribo-pentofuranosyl）uracil（EUrd）是一种新型的多功能抗肿瘤核苷类抗代谢药。以1-O-乙酰基-2，3，5-三-O-苯甲酰基-3-C-乙炔基-α，β-D-核糖呋喃戊糖（6）和双（三甲基硅烷基）尿嘧啶为原料，在三氟甲磺酸三甲基硅烷基酯存在下，在乙腈中进行缩合反应，然后用NH3/MeOH脱苯甲酰化，以高产率合成了EUrd。在体外肿瘤细胞生长抑制活性的EUrd对14人实体瘤细胞系进行了比较5-氟尿嘧啶（FUrd），2 '-脱氧-5-氟尿嘧啶（FdUrd），5-氟尿嘧啶（5-FU）作为阳性对照。除人胰腺PANC-1细胞外，EUrd对本研究中检查的几乎所有肿瘤细胞系都是非常有效的肿瘤细胞生长抑制剂，并且EUrd的效力比5-FU强约6至650倍，与FUrd和FdUrd相当。当连续几天每天静脉内给予2 mg/kg剂量时，EUrd还显示出对裸鼠异种移植的人肿瘤的强效抗肿瘤活性。版权所有（C）1996 Elsevier Science Ltd
1-(3-C-Ethynyl-beta-D-ribo-pentofuranosyl)uracil (EUrd) has been designed as a potential multifunctional antitumor nucleoside antimetabolite. EUrd was synthesized by condensation of 1-O-acetyl-2,3,5-tri-O-benzoyl-3-C-ethynyl-alpha,beta-D-ribo-pentofuranose (6) and bis(trimethylsilyl)uracil in the presence of trimethylsilyl triflate in CH3CN in good yield, followed by debenzoylation with NH3/MeOH. In vitro tumor cell growth inhibitory activity of EUrd against 14 human solid tumor cell lines was compared with 5-fluorouridine (FUrd), 2'-deoxy-5-fluorouridine (FdUrd), and 5-fluorouracil (5-FU) as positive controls. EUrd was a quite potent tumor cell growth inhibitor against almost ail the tumor cell lines examined in this study except for human pancreas PANC-1 cells, and the potency of EUrd is about 6 to 650 times stronger than that of 5-FU and comparable to that of FUrd and FdUrd. EUrd showed also potent antitumor activity against human tumors as xenografts in nude mice when given in a daily intravenous dose of 2 mg/kg on consecutive days. Copyright (C) 1996 Elsevier Science Ltd