Dihydropyrazine derivatives as a new type of DNA strand breaking agent.
Dihydropyrazine derivatives as a new type of DNA strand breaking agent.
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二氢吡嗪衍生物作为一种新型DNA链断裂剂。
DOI：
10.1248/bpb.19.1261
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发表时间：
1996
影响因子：
2
通讯作者：
K. Watanabe
中科院分区：
文献类型：
--
作者：
T. Yamaguchi;N. Kashige;N. Mishiro;F. Miake;K. Watanabe
研究了2，3-二氢-5，6-二甲基吡嗪（3），2，3-二氢-2，5，6-三甲基吡嗪（4），2，3-二氢-2，2，5，6-四甲基吡嗪（5），反式-2，3-二甲基-5，6，7，8，9，10-六氢喹喔啉（6），使用质粒pBR 322 ccc-DNA作为底物，通过琼脂糖凝胶电泳测试其顺式化合物（7）以及6和7的混合物（8）。Cu ~（2+）对DNA链断裂活性的影响顺序为（7）>（8）>或=（5）>（2）>（6）>（4）>或=（1）>或=（3）。2，5-双（D-阿拉伯基-四羟基丁基）-2，5-二氢吡嗪（1）和2，5-二氢-3，6-二甲基吡嗪（2）已经在先前的论文中描述了DNA断裂活性。活性被认为是由于二氢吡嗪骨架，除了在水溶液中形成的活性氧自由基。在二氢吡嗪骨架上引入一个甲基基团，提高了二氢吡嗪衍生物的活性。讨论了二氢吡嗪衍生物，特别是在Cu ~（2+）存在下引起DNA链断裂的可能化学基础。
The DNA strand-breaking activity of some dihydropyrazine derivatives, 2,3-dihydro-5,6-dimethylpyrazine (3), 2,3-dihydro-2,5,6-trimethylpyrazine (4), 2,3-dihydro-2,2,5,6-tetramethylpyrazine (5), trans-2,3-dimethyl-5,6,7,8,9, 10-hexahydroquinoxaline (6), its cis-compound (7) and the mixture of 6 and 7 (8) was tested by agarose gel electrophoresis using plasmid pBR322 ccc-DNA as a substrate. The order of DNA strand-breaking activity in the presence of Cu2+ was (7) > (8) > or = (5) > (2) > (6) > (4) > or = (1) > or = (3). 2,5-Bis(D-arabino-tetrahydroxybutyl)-2,5-dihydropyrazine (1) and 2,5-dihydro-3,6-dimethylpyrazine (2) have already been described in terms of DNA breaking activity in a previous paper. The activity was suggested to be due to the dihydropyrazine skeleton, in addition to active oxygen radicals formed in an aqueous solution. The introduction of a methyl group to the dihydropyrazine skeleton enhanced the activities of dihydropyrazine derivatives. The possible chemical basis for DNA strand breakage by dihydropyrazine derivatives, especially in the presence of Cu2+, was discussed.