摘要
目的研究多芳基取代蝶啶类化合物的合成及其抗肿瘤活性.方法由4,6-二氨基-5-亚硝基嘧啶衍生物与对-氨基苯乙腈衍生物通过环化合成目的物;采用MTF法测定目的物的抗肿瘤活性.结果设计、合成了9个新化合物(Ⅰ～Ⅲ),其结构经元素分析、IR,HNMR和MS等确定.化合物Ⅰ～Ⅲ的体外抗肿瘤活性较明显.结论化合物Ⅰ～Ⅲ显示了一定的体外抗肿瘤活性,但它们与小牛胸腺DNA之间并无明显作用,提示可能是通过抑制二氢叶酸还原酶(DHFR)或其他叶酸依赖性酶而起抗肿瘤作用.
Aim To study the synthesis and antitumour activities of some aryl-substituted pteridines.
Methods A series of aryl-substituted pteridines were synthesized from 4,6-diamino-5-nitrosopyrimidines by
cyclization with 4-aminophenylacetonitriles. The antitumour activities were tested by MTT method. Results
Nine new compounds (Ⅰ-Ⅲ) were synthesized and their stmctures were characterized by EA, IR, ~1HNMR and
MS spectra. Compounds Ⅰ -Ⅲ showed antitumour activities in vitro. Conclusion Compounds Ⅰ-Ⅲ showed
remarkable antitumour activities in vitro. No interaction was determined between the title compounds and calf
thymus DNA. It indicated that these compounds possibly inhibit dihydrofolate reductase (DHFR) or other
enzymes on which folic acid depends.
出处
《药学学报》
CAS
CSCD
北大核心
2004年第5期342-347,共6页
Acta Pharmaceutica Sinica
基金
国家自然科学基金(20272085)
广东省自然科学基金(021770)
关键词
多芳基
蝶啶类化合物
药物合成
抗肿瘤活性
测定
pteridines
synthesis
antitumour activity
methotrexate
dihydrofolate reductase
