光学纯脱氢枞胺杂环衍生物与DNA作用及初步细胞毒活性

Interaction of Optically Pure Dehydroabietylamine Heterocyclic Derivatives with DNA and Preliminary Cytotoxic Activity

根据活性叠加原理,在天然产物松香的改性产品光学纯脱氢枞胺(1)的B环和C环中引入不同的芳香杂环,合成了三个光学纯脱氢枞基杂环衍生物,乙酰脱氢枞胺-6,7-(3-巯基)-1,2,4-三嗪(5)、乙酰脱氢枞胺-6,7-吲哚(7)和12-(2-氨基噻唑)乙酰脱氢枞胺(10).荧光光谱和圆二色谱分析证明,化合物5、7和10均能够与DNA发生作用,且作用强度为5>10>7.凝胶电泳实验结果表明, 5、7和10都能够对p BR 322质粒DNA进行单链切割且5的切割能力最强.另外,脱氢枞胺及化合物5、7和10与氯化铜的复配物(32 μmol/L)对人乳腺肿瘤细胞MCF-7的增殖抑制率,分别为86.0%(1),86.7%(5), 34.4%(7)和0 (10).

Three optically pure dehydroabietylamine derivatives, acetyldehydroabietylamine-6,7-(3-mercapto)-1,2,4-triazine(5), acetyldehydroabietylamine-6,7-indole(7) and 12-(2-aminothiazole)-acetyldehydroabietylamine(10), were obtained by introducing different aromatic heterocycles into the B and C rings of optically pure dehydroabietylamine, which is derived from natural product of rosin, according to superposition principle of activity groups. The results of fluorescence spectroscopy and circular dichroism studies indicate that 5, 7 and 10 could interact with DNA, and the binding ability followed the order 5>10>7. Gel electrophoresis experiments suggest that 5, 7 and 10 could scissor pBR 322 plasmid DNA into single strands and 5 was the strongest cutter. In addition, the inhibitory rates of dehydroabietylamine and its derivatives 5, 7 and 10 combined with copper chloride(32 μmol·L-1) on the proliferation of human breast cancer cells MCF-7 were 86.0%(1), 86.7%(5), 34.4%(7) and 0(10), respectively.