一种天然产物Wangzaozin A的细胞毒活性(英文)

Cytotoxic Activity of a Natural Product Wangzaozin A

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WangzaozinA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WangzaozinA分子的静电位(MEP)进行理论计算.MEP三维图表明,在WangzaozinA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.

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 I 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.