丹参二萜醌的细胞毒活性及构效关系研究

Structure-Cytotoxic Activity Relationships of Diterpenoid Tanshinones from Salvias

目的 :丹参二萜醌的结构 -细胞毒活性的关联与探讨。方法 :应用 CHARM( Chemistry at HarvardMacro Molecular Mechanics)力场 ,用 powell方法优化本文涉及的丹参二萜醌及其类似物分子的几何构型 ,经优化后的分子构象采用 quanta软件包作 CNDO计算 ,以获取量子化学参数 ,并对这些参数进行分析。结果 :A环是芳环的丹参酮也包栝三环二萜凡具有平面环系统结构的均有可能对小鼠淋巴白血病细胞显示明显的细胞毒活性。在二氢呋喃环的氧原子 -3(如二氢丹参酮 - 、隐丹参酮 )较之含呋喃环氧原子 -3的丹参酮其局部电荷更负 ,因而也就使化合物具有更大的极性从而增强了细胞毒性。具有对称结构的含 1 ,4对萘醌生色团的丹参新醌 A或B较 1 ,2邻萘醌的如 Ro-0 90 6 80和二氢丹参酮 - 的细胞毒活性均显著降低。所有丹参酮及其类似物的疏水基团均远远多于亲水基团 ,因此它们均不溶于水 ,但可在水中以某种方式形成胶体颗粒 ,其中的一些参数如偶极距、范特华力、亲水指数 ,均可影响到它们的疏水相互作用。丹参酮 - 本身细胞毒活性很低 ,但通过 Mannich反应 ,在呋喃环上引进含氮杂环后其对

AIM Structure-Cytotoxic activity relationship and three -dimensional structures of diterpenoid tanshinones from Salvias have been studied.METHODS Quantum mechanics program of CHARMM (Chemistry at Harvard Macro Molecular Mechanics) force field has been used for optimizing the molecule geometry of all tanshinones analogues. All these optimized conformations of compounds adopted quanta software package through the CNDO calculation, to get all these quantum mechanics parameters. CONCLUSION Several important conclusions have been made as follows: 1.The tanshinone having an aromatic ring A has a planar ring system, and its cytotoxicity is much stronger than that of the tanshinone having an alicyclic ring A. 2.The partial atomic charges of ether-type oxygen-3 (such as dihydrotanshinone-Ⅰ; cryptotanshinone) are more negative than those of the tanshinones which have a furan ring (tanshinone-Ⅰ;tanshinone-ⅡA),the more negative partial atomic charge of oxygen-3 will increase the cytotoxicity and the polarity of tanshinone having a furan ring. 3. The system in a compound (1,4 naphtho-quinone) would decrease molecular polarity and its cytotoxic activity in comparison with the compound 1,2 naphoto-quinone. 4. All the tanshinone analogues are more hydrophobic than hydrophilic it can not be dissolving in water media, but they may form colloidal particles which arises from the hydrophobic interaction.