夹竹桃叶中的甾体类化学成分及其细胞毒活性的研究
摘要
本论文由三个部分组成：第一部分概述了夹竹桃的研究进展；第二部分是夹竹桃(Nerium indicum)叶中的甾体类化学成分研究；第三部分是夹竹桃中分离得到的化合物的细胞毒活性测试及构效关系探讨。
夹竹桃(Nerium indicum. Mill),为夹竹桃属常绿灌木。夹竹桃的化学成分有强心苷、孕甾烷、萜类以及黄酮等,药理活性报道有强心、抗肿瘤、抗炎、镇静催眠、抗菌作用等。
对夹竹桃(Nerium indicum)叶进行化学成分研究共分离得到14个化合物。其中包含1个新的孕甾烷类化合物,命名为14α,16-dihydroxy-3-oxo-γ-lactone-pregn-4-en-21-oic acid(16β,17α)及13个已知强心苷及苷元化合物,分别是夹竹桃苷(JZT-2),夹竹桃苷元(JZT-3), neriosid (JZT-4), nerigoside (JZT-5), JZT-6, JZT-8,欧夹竹桃昔乙(JZT-9),奥多诺苷-A (JZT-14),3β-hydroxy-5β-carda-8,14,20,(22)-trienolid (JZT-17),奥多诺苷-H(JZT-19),去乙酰欧夹竹桃苷丙(JZT-21),欧夹竹桃苷元乙(JZT-25),3-hydroxy-5β-8,14-epoxy-card-20(22)enolid (JZT-28)。
我们对分离得到的化合物进行了体外细胞毒活性测试,所用细胞株为HeLa细胞。试验结果表明,大部分化合物显示具有很强的细胞毒活性,其中JZT-14活性最强,IC50值为9.7 nM。强心苷元A／B环为顺式稠合细胞毒活性略优于反式稠合；C／D环顺式稠合有很强的细胞毒活性,若为反式或脱水成双键,则细胞毒活性消失；C16位的氢被羟基或者乙酰基取代时,对活性影响不大,若与C17位之间形成双键则活性降低；苷的活性优于苷元。
This dissertation consisted of three chapters:Chapter one was the advances of the studies on the plant of Nerium indicum. Mill. Chapter two was study on steroids of the leaves Nerium indicum plant. Chapter three was the cytotoxicity evaluation and SAR discussion of compounds isolated from the leaves of Nerium indicum. Mill.
Nerium indicum. Mill(Nerium oleander L) is Apocynaceae, a rare evergreen shrub. It includes many chemical constituents, such as cardiac glycosides, pregnanes, terpenes and flavonoids etc.. The plant which has been reputed as therapeutic agents, has varieties of biological activities including heart failure, cancer, anti-neoplastic, anti-inflammatory, sedation, anti-bacterial and anthelminthic effects.
Phytochemical studies on Nerium indicum. Mill have led to the isolation fourteen compounds, including one new pregnane,14α,16-dihydroxy-3-oxo-γ-lactone-pregn-4-en-21-oic acid (16β,17α) (JZT-27), and thirteen known cardiac glycosides:oleandrin (JZT-2), oleandrigenin (JZT-3), neriosid (JZT-4), nerigoside (JZT-5),16,17-didehydrosomalin (JZT-6), oleaside A (JZT-8), adynerin (JZT-9), odoroside-A (JZT-14),3β-hydroxy-5β-carda-8β,14β,20,(22)-trienolid (JZT-17), odoroside H (JZT-19), deacetyloandrin (JZT-21), adynerigenin (JZT-25),3β-hydroxy-5α-8β,14β-epoxy-card-20(22)-enolid (JZT-28) were isolated and indentified by comparison of their physical and spectral data with those reported in the literature.
All the isolated compounds were tested for the cytotoxic activity against HeLa cell. Most of them exhibited strong cytotocity and JZT-14 had the strongest cytotoxicity with IC50 9.7 nM. Their structure-activity relationships were discussed. Cis A/B ring of cardiac aglycones is stronger than trans; cis C/D ring has strong cytotoxicity, trans or unsaturated C/D ring has no cytotoxicities; the hydroxyl or acetyl substituted at C16 do not change their cytotoxicities; the double bond between C16 and C17 heavily decreased their cytotoxicities; and 3-O-glycosidization significantly increase their cytotoxicities.
夹竹桃(Nerium indicum. Mill),为夹竹桃属常绿灌木。夹竹桃的化学成分有强心苷、孕甾烷、萜类以及黄酮等,药理活性报道有强心、抗肿瘤、抗炎、镇静催眠、抗菌作用等。
对夹竹桃(Nerium indicum)叶进行化学成分研究共分离得到14个化合物。其中包含1个新的孕甾烷类化合物,命名为14α,16-dihydroxy-3-oxo-γ-lactone-pregn-4-en-21-oic acid(16β,17α)及13个已知强心苷及苷元化合物,分别是夹竹桃苷(JZT-2),夹竹桃苷元(JZT-3), neriosid (JZT-4), nerigoside (JZT-5), JZT-6, JZT-8,欧夹竹桃昔乙(JZT-9),奥多诺苷-A (JZT-14),3β-hydroxy-5β-carda-8,14,20,(22)-trienolid (JZT-17),奥多诺苷-H(JZT-19),去乙酰欧夹竹桃苷丙(JZT-21),欧夹竹桃苷元乙(JZT-25),3-hydroxy-5β-8,14-epoxy-card-20(22)enolid (JZT-28)。
我们对分离得到的化合物进行了体外细胞毒活性测试,所用细胞株为HeLa细胞。试验结果表明,大部分化合物显示具有很强的细胞毒活性,其中JZT-14活性最强,IC50值为9.7 nM。强心苷元A／B环为顺式稠合细胞毒活性略优于反式稠合；C／D环顺式稠合有很强的细胞毒活性,若为反式或脱水成双键,则细胞毒活性消失；C16位的氢被羟基或者乙酰基取代时,对活性影响不大,若与C17位之间形成双键则活性降低；苷的活性优于苷元。
This dissertation consisted of three chapters:Chapter one was the advances of the studies on the plant of Nerium indicum. Mill. Chapter two was study on steroids of the leaves Nerium indicum plant. Chapter three was the cytotoxicity evaluation and SAR discussion of compounds isolated from the leaves of Nerium indicum. Mill.
Nerium indicum. Mill(Nerium oleander L) is Apocynaceae, a rare evergreen shrub. It includes many chemical constituents, such as cardiac glycosides, pregnanes, terpenes and flavonoids etc.. The plant which has been reputed as therapeutic agents, has varieties of biological activities including heart failure, cancer, anti-neoplastic, anti-inflammatory, sedation, anti-bacterial and anthelminthic effects.
Phytochemical studies on Nerium indicum. Mill have led to the isolation fourteen compounds, including one new pregnane,14α,16-dihydroxy-3-oxo-γ-lactone-pregn-4-en-21-oic acid (16β,17α) (JZT-27), and thirteen known cardiac glycosides:oleandrin (JZT-2), oleandrigenin (JZT-3), neriosid (JZT-4), nerigoside (JZT-5),16,17-didehydrosomalin (JZT-6), oleaside A (JZT-8), adynerin (JZT-9), odoroside-A (JZT-14),3β-hydroxy-5β-carda-8β,14β,20,(22)-trienolid (JZT-17), odoroside H (JZT-19), deacetyloandrin (JZT-21), adynerigenin (JZT-25),3β-hydroxy-5α-8β,14β-epoxy-card-20(22)-enolid (JZT-28) were isolated and indentified by comparison of their physical and spectral data with those reported in the literature.
All the isolated compounds were tested for the cytotoxic activity against HeLa cell. Most of them exhibited strong cytotocity and JZT-14 had the strongest cytotoxicity with IC50 9.7 nM. Their structure-activity relationships were discussed. Cis A/B ring of cardiac aglycones is stronger than trans; cis C/D ring has strong cytotoxicity, trans or unsaturated C/D ring has no cytotoxicities; the hydroxyl or acetyl substituted at C16 do not change their cytotoxicities; the double bond between C16 and C17 heavily decreased their cytotoxicities; and 3-O-glycosidization significantly increase their cytotoxicities.
引文
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