石斛兰和两种瓜馥木属植物化学成分及其药理活性研究

发布时间：2018-05-06 14:46

  本文选题：石斛兰 + 瓜馥木　； 参考：《海南师范大学》2017年博士论文

【摘要】：石斛兰是兰科石斛属植物,全株既可入药也可用于观赏。在海南有许多石斛兰种植户,他们主要是以鲜花销售为主,产业效益不高。石斛的鲜花被采割三年后,其根茎往往会被拔除,为了更充分开发利用石斛兰的其他价值,我们对其根茎进行了系统的化学成分及其药理活性研究。通过系统的分离鉴定,从石斛兰茎中共分离鉴定63个化合物(1-63),主要为菲类,内酯类以及苷类化合物;其中新化合物14个。63个化合物中有3对对映异构体(1和2,34和35,36和37),通过ECD计算及X-ray单晶衍射确定了这3对对映异构体的绝对构型;通过X-ray单晶衍射确定了新化合物3和32的绝对构型。抗肿瘤活性测试表明化合物1和2对人宫颈癌细胞(HeLa),人乳腺癌细胞(MCF-7),人肺癌细胞(A549)具有较强细胞毒活性,其IC50值分别为9.8,9.4和9.9μM。抗植物病原菌活性测试发现其中二苯基乙烷类化合物(17-21)具有较强且广谱的抗菌活性。另外,化合物39,41,43,53和54同样显示较为广谱的抗菌活性。瓜馥木作为传统的中药材,用来治疗关节疼痛已有悠久的历史;海南是关节炎类疾病多发地区,尤其是类风湿性关节炎。为了寻找有效的抗类风湿关节炎活性分子,我们对两种瓜馥木属植物(瓜馥木和毛瓜馥木)进行了系统的化学成分及抗类风湿关节炎活性研究。从两种瓜馥木属植物中共分离鉴定了133个化合物(64-196),倍半萜类和生物碱类是这两种植物的主要成分,其中从瓜馥木中分离鉴定新化合物17个,从毛瓜馥木中分离鉴定新化合物5个;新化合物大多为倍半萜类化合物。其中化合物64为首次发现具有五元醚环结构的愈创木烷型倍半萜,化合物65,67,68以及70为较少见的降碳类倍半萜;化合物72与73是首次发现在6位形成羰基的愈创木烷型倍半萜。对瓜馥木与毛瓜馥木中大部分化合物进行了抗类风湿关节炎活性测试,结果表明瓜馥木乙醇提取物具有一定的滑膜细胞抑制作用;化合物72与73具有很强的滑膜细胞抑制作用,其IC50值分别为1.0μM和1.2μM,与阳性对照甲氨蝶呤(1.0μM)相当;而其余倍半萜类化合物65,67,68,70,71,81,87-89,167,183也具有一定的滑膜细胞抑制作用,其IC50值范围为10.1 60.2μM。构效关系研究表明愈创木烷型倍半萜的6位酮羰基为其活性官能团。对活性化合物72进行了抗类风湿关节炎活性机制研究,结果显示72具有较好的抗类风湿关节炎活性。
[Abstract]:Dendrobium is a plant of Dendrobium in Orchidaceae. In Hainan there are many Dendrobium growers, they are mainly to sell flowers, industrial efficiency is not high. The rhizome of Dendrobium will often be uprooted three years after it has been harvested. In order to make full use of the other value of Dendrobium, the chemical constituents and pharmacological activities of Dendrobium rootstock were studied systematically. A total of 63 compounds, mainly phenanthrene, lactone and glycosides, were isolated from Dendrobium stem. Among them, 14 new compounds have 3 enantiomers, 3 enantiomers, 35,36 and 37, respectively. The absolute configuration of the 3 enantiomers has been determined by ECD calculation and X-ray single crystal diffraction. The absolute configurations of new compounds 3 and 32 were determined by X-ray single crystal diffraction. The antitumor activity test showed that compound 1 and 2 had strong cytotoxic activity against human cervical cancer cell line, human breast cancer cell line MCF-7 and human lung cancer cell line A549. The IC50 values of compounds 1 and 2 were 9.89.4,9.9 渭 m, respectively. It was found that diphenyl ethane compound 17-21) had strong and broad-spectrum antibacterial activity. In addition, compounds 39, 41, 43, 53 and 54 also showed broad-spectrum antimicrobial activity. As a traditional Chinese medicine, Guaofoumu has a long history of treating joint pain. Hainan is a region where arthritis diseases are frequent, especially rheumatoid arthritis. In order to find effective anti-rheumatoid arthritis (RA) active molecules, we studied the chemical constituents and anti-rheumatoid arthritis activities of two species of the genus Cucurbita. A total of 133 compounds, including sesquiterpenoids and alkaloids, were isolated and identified from two species of the genus Cucurbita, and 17 new compounds were isolated and identified from the plants. Five new compounds were isolated and identified from Cucurbita pubescens, and most of them were sesquiterpenoids. Compounds 64 were the first to find quacomeric sesquiterpenes, compounds 65O67N68 and 70 were rare sesquiterpenes, and compounds 72 and 73 were the first to find guaiacane sesquiterpenes forming carbonyl groups at 6 sites. The antirheumatoid arthritis activity of most compounds from Cucurbita and Cucurbita was tested. The results showed that the ethanol extract of Flos Guafordii had a certain inhibitory effect on synovial cells, and compounds 72 and 73 had strong inhibitory effect on synovial cells. Their IC50 values were 1.0 渭 M and 1.2 渭 M, respectively, which were comparable to those of the positive control group (methotrexate 1.0 渭 M), while the other sesquiterpenoid compounds 65-677-687071C 81-81-87-89167183 also had a certain inhibitory effect on synovial cells, and their IC50 values ranged from 10.10. 60.2 渭 m to that of other sesquiterpenoid compounds. The results of structure-activity relationship showed that 6 ketone carbonyl groups of sesquiterpenes of guaiacane type were their active functional groups. The mechanism of anti-rheumatoid arthritis activity of active compound 72 was studied. The results showed that 72 had good anti-rheumatoid arthritis activity.
【学位授予单位】：海南师范大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R284;R285
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本文编号：1852727