物理化学学报 >> 2009, Vol. 25 >> Issue (09): 1749-1755.doi: 10.3866/PKU.WHXB20090824

研究论文 上一篇    下一篇

一种天然产物Wangzaozin A的细胞毒活性

杨相艳, 张宜恒, 丁兰, 汪汉卿   

  1. 青岛科技大学化学与分子工程学院, 山东 青岛 266042|青岛科技大学国际学院, 山东 青岛 266061|西北师范大学生命科学学院, 兰州730070|中国科学院兰州化学物理研究所, 兰州 730000
  • 收稿日期:2009-01-24 修回日期:2009-05-30 发布日期:2009-09-03
  • 通讯作者: 张宜恒 E-mail:yhzhang@ustc.edu.cn

Cytotoxic Activity of a Natural ProductWangzaozin A

YANG Xiang-Yan, ZHANG Yi-Heng, DING Lan, WANG Han-Qing   

  1. College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042, Shandong Province, P. R. China|International College, Qingdao University of Science and Technology, Qingdao 266061, Shandong Province, P. R. China|College of Life Science, Northwest Normal University, Lanzhou 730070, P. R. China|Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, P. R. China
  • Received:2009-01-24 Revised:2009-05-30 Published:2009-09-03
  • Contact: ZHANG Yi-Heng E-mail:yhzhang@ustc.edu.cn

摘要:

从总序香茶菜Isodon racemosa (Hemsl) Hara植物中分离得到一个对人类肿瘤细胞Bel-7402和HD-8910具有毒活性的对映-贝壳衫烷型二萜Wangzaozin A化合物(1). 应用密度泛函理论(DFT)B3LYP方法, 对该分子的几何构型进行优化, 结果表明用B3LYP/6-31G(d)优化的几何参数与它的X射线衍射结构参数基本一致. 在优化的几何构型基础上, 采用规范不变原子轨道(GIAO)法, 在B3LYP理论水平分别用6-31G(d), 6-31G(d,p), 6-31+G(d,p)和6-31++G(d,p)基组进行核磁共振(NMR)化学位移值计算, 预测的1H和13CNMR化学位移值与实验值吻合; 统计误差分析表明, 用B3LYP/6-31G(d)优化的分子构型接近实际的分子构型. 因此, DFT方法适用这一类型化合物的构型和NMR参数进行预测. 在几何优化的基础上, 在B3LYP/6-31G(d)水平上, 对Wangzaozin A分子的静电位(MEP)进行理论计算. MEP三维图表明, 在Wangzaozin A分子中α-亚甲基环戊酮的羰基和羟基附近出现富电子区域(负电位), 起着供电子作用, 与受体的正电子区域结合. 这些结果从理论上支持了α-亚甲基环戊酮结构是一种抗肿瘤活性中心的看法.

关键词: 密度泛函理论, 质子化, Wangzaozin A, 核磁共振, 分子静电位

Abstract:

Wangzaozin A (1) is an ent-kaurane diterpenoid isolated from Isodon racemosa (Hemsl) Hara. This natural product exhibits significant cytotoxicity against human Bel-7402 and HO-8910 tumor cells. The structural parameters of compound 1 from X-ray diffraction were compared with those from theoretical calculations at B3LYP/6-31G(d) level compound and the theoretical results were found to be in accordance with the experimental data. The 1H and 13C NMR chemical shifts of compound 1 were also calculated using the gauge independent atomic orbital (GIAO) method at the B3LYP level with the 6-31G(d), 6-31G(d,p), 6-31+G(d,p), and 6-31++G(d,p) basis sets. Results showed that the calculated NMR data for the geometrical conformation optimized using the B3LYP/6-31G(d) basis set are the most accurate by comparison to experimental data. The geometrical conformation optimized using the B3LYP/6-31G(d) basis set, therefore, approximates the real geometric structure of compound 1 most accurately. Statistical error analysis for the theoretically predicted δH and δC values versus experimentally observed values for compound 1 was conducted. A molecular electrostatic potential (MEP) map was used in an attempt to identify key features of the diterpenoid Wangzaozin A to account for its anti-tumor activity. MEP investigations reveal that compound 1, which shows anti-tumor activity, possesses electron-rich regions that extend over the hydroxyl and carbonyl groups of compound 1.

Key words: Density functional theory, Protonation, Wangzaozin A, Nuclear magnetic resonance, Molecular electrostatic potential

MSC2000: 

  • O641