苦蘵中Withanolide型化合物的化学成分研究

【作者】 贺庆平；

【导师】 罗杰英； 贺福元； 胡立宏；

【作者基本信息】 湖南中医药大学 ， 中药学， 2007， 硕士

【摘要】 Withanolide型化合物是一类具有28个碳原子的麦角甾烷型的化合物,其特有的结构是22位与26位碳连接形成一个6内酯环的侧链。Withanolides不仅可以用来表示麦角甾烷型的22,26-内酯,也可以用来表示所有生源相关的化合物。前者是经典型的Withanolide型化合物,后者是非经典型的Withanolide型化合物。这些化合物主要分布在茄科的几个属中,如Physalis、Withania、Ajuga、Datura、Jaborosa、Dunalia、Salpichroa、Deprea、Solanum、Vassobia、Exodeconus、Hyoscyamus、Iochroma、Discopodium等。其中Physalis(酸浆属)是这类化合物的重要来源。该属植物在世界许多国家具有悠久的药用历史,并且已成为近年来临床研究正在进行的项目。在初步的研究中,已经证实了该属植物对各种肿瘤和白血病细胞有胞毒性,并且还具有抗病原微生物的作用。本课题选用了一种典型的茄科酸浆属植物：Physalis angulata苦蘵(重庆南川县)对此种植物的Withanolide类型化学成分进行系统研究,共分离得到Withanolide型化合物11个,他们分别是physagulins L-0 (1-4), withagulatin A(5), physagulin K(6), withaminimin(7), physagulin J(8), physagulin B(9), pubesenolide(10), physagulin D(11).通过文献检索及对照,发现化合物1、2、3、4为新化合物。以上化合物的结构鉴定通过IR, 1D,2D-NMR, HRMS,旋光等方法进行确定。对上述的化合物进行抗肿瘤活性测定,发现化合物5和9对人乳腺癌病毒(HCT-116)和非人小肺癌病毒(NCI-H460)有很好的抑制作用。化合物5IC50分别是1.64±0.06μM和1.40±0.04μM,化合物9IC50分别是2.11±0.1μMM和0.43±0.02μM。更多还原

【Abstract】 Withanolides are structurally diverse steroids with an ergostane skeleton in which C (22) and C (26) are oxidized to form a d-lactone. Withanolides not only represent a d-lactone with C (22) and C (26) oxidized, but also represent all relatived biosynthetic pathways compounds. The former is normal withanolide compounds, the latter is non-normal ones. These compounds are specific for the Solanaceae family, and, in particular, for the genera Physalis、Withania、Ajuga、Datura、Jaborosa、Dunalia、Salpichroa、Deprea、Solanum、Vassobia、Exodeconus、Hyoscyamus、Iochroma、Discopodium and so on. Physalis is the important origin for these compounds. The genera plants have been used in various countries in popular medicine as a treatment for different illnesses, and have become a clinical research project recently. In preliminary research, the results showed that the raw extract of the material possessed anti-tumor activities and anti-leukaemia cell lines activity. In present work, we choosed two kinds of physalis plants:Physalis angulata (Nanchuan County, Chongqing city).The chemical investigation of the methanol extract of its aerial part led to afford 11 withanolides:physagulins L-O (1-4), withagulatin A(5), physagulin K(6), withaminimin(7), physagulin J(8), physagulin B(9), pubesenolide(10), physagulin D(11)。 Compounds 1、2、3、4 are new chemicals. The structures of these compounds were determined by spectral data including IR,1D, 2D-NMR and HRMS spectra. Compounds 1-11 were tested for their antiproliferative activity towards the human colorectal carcinoma (HCT-116) cell line and human non-small cell lung cancer (NCI-H460) cell line. Compound 5 exhibited the highest activity against the HCT-116 cell line, with an IC50 value of 1.64±0.06μM, and compound 9 exhibited the highest activity to NCI-H460 cell line, with an IC50 value of 0.43±0.02μM.更多还原