β-咔啉-3-甲酰胺类衍生物的合成及与DNA的作用

β-咔啉-3-甲酰胺类衍生物的合成及与DNA的作用

林伟, 肖苏龙, 杨铭^*

北京大学天然药物及仿生药物国家重点实验室, 北京 100083

收稿日期:2001-04-26 修回日期:2001-06-20 出版日期:2001-09-15 发布日期:2001-09-15
通讯作者: 杨铭*

The Syntheses of β-Carboline-3-carboxamides Derivatives and Their Interaction with DNA

Lin Wei, Xiao Sulong, Yang Ming^*

National Research Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100083

Received:2001-04-26 Revised:2001-06-20 Online:2001-09-15 Published:2001-09-15
Contact: Yang Ming*

摘要/Abstract

摘要： 合成系列β-咔啉-3-甲酰胺类化合物, 并研究其与CT-DNA的作用。以l-色氨酸为原料, 设计并合成β-咔啉-3-甲酰胺类化合物, 利用粘度滴定、Tm(解链温度)测定及紫外光谱滴定法以及微量量热等方法测定其与CT-DNA的作用。在与CT-DNA的相互作用中, 它们均能引起CT-DNA Tm的改变; 粘度滴定实验表明该系列化合物与DNA以嵌插方式作用; 紫外光谱滴定法表明该系列化合物与DNA的结合强度是有差异的, 这与抗肿瘤筛选的结果一致; 微量量热研究结果表明这类化合物与DNA的作用是熵驱动的。该β-咔啉新衍生物是以DNA为靶, 并通过与DNA碱基的嵌插产生生物效应。

关键词: β-咔啉3-甲酰胺类衍生物, 化学合成, CT-DNA

Abstract: To study the interactions of these compounds with calf thymus DNA(CT-DNA), seven β-carboline-3-carboxamides were designed and synthesized. The interactions of these compounds with CT-DNA were determined by the viscometric titration assay and Tm (melting temperature) value assay. Binding strengths were evaluated by spectrophotometric titration experiment and microcalorimetric measurement. The interactions of these compounds were tested with CT-DNA. It was showed that all of these compounds were able to change the Tm value of CT-DNA. The results of viscometric titration assay indicated that these compounds interacted with CT-DNA by intercalation. Spectrophotometric titration experiment showed that the binding strengths of these compounds with CT-DNA were different, which was well in agreement with the cell culture results. The binding was driven by entropy according to the results of the microcalorimetric measurement. This series of β-carboline-3-carboxamides is DNA targeting compounds. Their obvious antitumor biological effect is based on the intercalation with DNA base-pairs.

Key words: β-Carboline-3-carboxamides, β-Carboline-3-carboxamides, Chemical synthesis, Chemical synthesis, CT-DNA, CT-DNA

Supporting:

^*This work was supported by National Natural Sciences Foundation of China (39870183), National Doctoral Foundation of China (9930) and Natural Science Foundation of Beijing.

林伟, 肖苏龙, 杨铭^*. β-咔啉-3-甲酰胺类衍生物的合成及与DNA的作用[J]. .

Lin Wei, Xiao Sulong, Yang Ming^* . The Syntheses of β-Carboline-3-carboxamides Derivatives and Their Interaction with DNA[J]. .

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