含嘧啶的α-亚甲基-γ-丁内酯的合成及细胞毒性研究

Synthetic and cytotoxic studies of alpha-methylene-gamma-butyrolactone bearing pyrimidines.

作者信息

Huang B R, Lee K H, Tseng T L, Wang H M, Chen C F, Tzeng C C

机构信息

School of Chemistry, Kaohsiung Medical College, Taiwan, Republic of China.

出版信息

Gaoxiong Yi Xue Ke Xue Za Zhi. 1993 Dec;9(12):707-11.

PMID:8207771

Abstract

A total of ten pyrimidine alpha-methylene-gamma-butyrolactones were synthesized as potential antitumor agents on the basis of their possible action as Michael acceptors for DNA/RNA and cellular enzymes. The synthesis of these heterocycles involved a convenient Reformatsky-type reaction of pyrimidinyl ketones with ethyl alpha-(bromomethyl)acrylate. The preliminary in vitro cytotoxic assay indicated that these synthetic compounds were essentially active against the growth of KB, Hep-2, HeLa and Colo-205 cells. Among them, 5'-biphenyl-5'-(uracil-1-ylmethyl)-2'-oxo-3'-methylenetetrahydr ofuran (5f) demonstrated to be the most potent antileukemic agent.

摘要

基于嘧啶α-亚甲基-γ-丁内酯作为DNA/RNA和细胞酶的迈克尔受体的可能作用，总共合成了十种嘧啶α-亚甲基-γ-丁内酯作为潜在的抗肿瘤剂。这些杂环的合成涉及嘧啶基酮与α-（溴甲基）丙烯酸乙酯的便捷Reformatsky型反应。初步的体外细胞毒性试验表明，这些合成化合物对KB、Hep-2、HeLa和Colo-205细胞的生长基本有活性。其中，5'-联苯基-5'-（尿嘧啶-1-基甲基）-2'-氧代-3'-亚甲基四氢呋喃（5f）被证明是最有效的抗白血病药物。