具有抗癌活性的新型硒杂环化合物的合成及其与牛血清蛋白的相互作用

doi:10.6023/A1202031

化学学报 ›› 2012, Vol. 70 ›› Issue (11): 1295-1303.DOI: 10.6023/A1202031 上一篇下一篇

研究论文

具有抗癌活性的新型硒杂环化合物的合成及其与牛血清蛋白的相互作用

罗懿^a, 陈填烽^a, 黄晓纯^a, 王弋^a, 黄荫成^b, 郑文杰^a

a 暨南大学化学系广州510632;
b 香港中文大学生命科学学院香港沙田

投稿日期:2012-02-03 修回日期:2012-02-14 发布日期:2012-02-14
通讯作者: 陈填烽, 郑文杰 E-mail:tchentf@jnu.edu.cn, tzhwj@jnu.edu.cn
基金资助:
教育部新世纪优秀人才支持计划(NCET 10-0119), 国家自然科学基金项目(Nos. 21071062, 20901030)和广东省科技攻关项目(No. 2008A030201020).

Synthesis, Anticancer Activity of a Novel Selenadiazole Derivative and Its Interaction with Bovine Serum Albumin

Luo Yi^a, Chen Tianfeng^a, Huang Xiaochun^a, Wang Yi^a, Wong Yumshing^b, Zheng Wenjie^a

a Department of Chemistry, Jinan University, Guangzhou 510632;
b School of Life Sciences, The Chinese University of Hong Kong, Hong Kong

Received:2012-02-03 Revised:2012-02-14 Published:2012-02-14
Supported by:
Project supported by New Century Excellent Talents in University (NCET 10-0119), the National Natural Science Foundation of China (Nos. 21071062 and 20901030), Key Project of Science and Technology Department of Guangdong Province (No. 2008A030201020).

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摘要/Abstract

合成了一种新的硒二唑衍生物4-(苯并[c][1,2,5]硒二唑-6-yl)苯-1,2-二氨基(BSBD). 研究了其抗肿瘤活性, 结果发现BSBD 具有很好的抗癌活性, 特别对Neuro-2a 小鼠脑神经瘤细胞表现出很好的选择性. 关于作用机制的研究发现,BSBD 可呈剂量效应的诱导肿瘤细胞中 Sub-G1 凋亡峰的累积、染色质固缩及凋亡小体的形成, 说明诱导细胞凋亡是BSBD 发挥抗肿瘤活性的主要机制. 进而应用紫外-可见吸收光谱、荧光光谱法、傅里叶红外光谱、圆二色光谱法研究了其与牛血清白蛋白(BSA)的相互作用. 采用位点结合模型公式和热力学公式计算了结合常数、结合位点数及结合力类型, 并用紫外-可见吸收光谱、红外光谱和圆二色光谱技术探讨了硒杂环化合物对牛血清白蛋白构象的影响. 结果表明:BSBD 能有效淬灭牛血清白蛋白的荧光强度, 其猝灭机理为静态猝灭, 主要作用力类型是氢键和范德华力. 而同步荧光、紫外-吸收示差光谱、红外光谱和圆二色光谱都进一步证明了BSBD 与BSA 结合后, 改变了BSA 的内部结构.

关键词: 硒杂环化合物, 抗肿瘤活性, 牛血清白蛋白, 相互作用, 荧光猝灭

A novel selenadiazol derivative (BSBD) has been synthesized, characterized and evaluated for its anticancer activity. The in vitro anticancer activities of BSBD were screened by MTT assay against various cancer cell lines and it was found that BSBD could effectively inhibit cancer cell growth, especially for Nuero-2a neuroblastoma cells. Further investigation on the action mode showed that BSBD could induce Sub-G1 peak accumulation, chromatin condensation and the formation of apoptotic body in a dose-dependent manner in cancer cells, indicating that induction of apoptosis is the main mechanism accounting for the action of BSBD. Moreover the interaction between BSBD and bovine serum albumin (BSA) was investigated by UV-Vis, fluorescence and circular dichroism spectrometry and FTIR. The binding constants, number of binding sites and type of binding force were calculated by applying the equation of site-binding model and thermodynamic equations. The results of UV-Vis, FTIR and circular dichroism spectrometry revealed that the major interaction mode between BSA and BSBD was static quenching, due to hydrogen bonding and van der Waals force. The results of spectroscopic characterization showed BSBD altered the chemical structure and conformation of BSA.

Key words: selenadiazole derivative, anticancer activities, bovine serum albumin, interation, fluorescence quenching

引用此文

罗懿, 陈填烽, 黄晓纯, 王弋, 黄荫成, 郑文杰. 具有抗癌活性的新型硒杂环化合物的合成及其与牛血清蛋白的相互作用[J]. 化学学报, 2012, 70(11): 1295-1303.

Luo Yi, Chen Tianfeng, Huang Xiaochun, Wang Yi, Wong Yumshing, Zheng Wenjie. Synthesis, Anticancer Activity of a Novel Selenadiazole Derivative and Its Interaction with Bovine Serum Albumin[J]. Acta Chimica Sinica, 2012, 70(11): 1295-1303.

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具有抗癌活性的新型硒杂环化合物的合成及其与牛血清蛋白的相互作用

Synthesis, Anticancer Activity of a Novel Selenadiazole Derivative and Its Interaction with Bovine Serum Albumin

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