大葉瓜馥木化學成分及其生物活性之研究

Chemical Constituents and Biological Investigations of Fissistigma latifolium

林佳貞

大葉瓜馥木 ； 化學成分 ； 生物活性 ； Biological ； Chemical Constituents ； Fissistigma latifolium

中國醫藥大學藥學系博士班學位論文

2013年

碩士

藍于琁

繁體中文

大葉瓜馥木(Fissistigma latifolium)為番荔枝科(Annonaceae)植物，屬於一種低海拔的灌木，主要分布在亞洲熱帶地區。過去的研究顯示了本屬植物具有眾多的生物鹼種類及多方面的藥理活性，如：鎮痛、抗發炎、抗菌、抗癌活性及心血管活性等，基於開發新醫藥資源的目的，本研究針對過去僅有少數文獻被報導的大葉瓜馥木(F. latifolium)進行活性成分的分離。 由F. latifolium全株甲醇萃取物分離得到十五個化合物，經由光譜分析及文獻比對後，確認了化合物的結構，包括七個alkaloid類化合物，分別為oxocrebanine (1)、lysicamine (2)、liriodenine (3)、atherospermidine (4)、aristolactam AIIIa (5)、goniothalactam (6)及piperlactam A (7)，五個flavonoid類化合物，分別為5,6,7-trimethoxyflavone (8)、2,5,6,7-tetramethoxyflavan(9)、 2-hydroxy-4,5,6-trimethoxydihydrochalcone (10)、4,6-dimethoxy- 2,5-quinodihydrochalcone (11)和[3-3′]bi-2-hydroxy-4,5,6-trimethoxy dihydrochalcone (12)，一個benzil類化合物，為2′-hydroxy-4′,5′,6′-trimethoxybenzil (13)，二個benzenoid類化合物，分別為vanillic acid (14)及benzaldehyde (15)，其中化合物(9)、(11)、(12)和(13)則是首次自從天然界分離得到之新化合物，而化合物(8)、(10)和(15)為首次從本屬植物中分離得到。 在生物活性試驗方面，化合物(9)對於fMLP(formyl-L-methionyl-L-leucyl-L-phenylalanine)誘導的嗜中性白血球超氧自由基(O2•-)生成作用顯示抑制之活性；化合物(11)對人類乳癌細胞（MDA-MB-231）具細胞毒殺活性。

Fissistigma latifolium (Annonaceae) is a climbing shrub found in low altitude forest and mainly distributed in tropical Asia. Previous studies showed that the Fissistigma genera has numerous classes of alkaloids and pharmacological activity， such as analgesic, anti-inflammatory, antimicrobial, anti-tumor and cardiovascular effects. In this study, active compounds were isolated and purified from F. latifolium in order to develop new medicine resources. There were fifteen compounds isolated from F. latifolium crude extracts, and their structures were established by NMR spectroscopy and references comparison. These compounds includ seven alkaloids, oxocrebanine (1), lysicamine (2), liriodenine (3), atherospermidine (4), aristolactam AIIIa (5), goniothalactam (6), piperlactam A (7); five flavonoids, 5,6,7-trimethoxyflavone (8), 2,5,6,7-tetramethoxyflavan (9)、2-hydroxy-4,5,6-trimethoxydihydrochalcone (10), 4,6-dimethoxy-2,5-quinodihydrochalcone (11), [3-3′]bi-2-hydroxy-4,5,6- trimethoxydihydrochalcone (12); one benzyl, 2′-hydroxy-4′,5′,6′- trimethoxybenzil (13) and two benzenoid, vanillic acid (14) and benzaldehyde (15). Compounds 9, 11, 12 and 13, were isolated from natural sources for the first time. Compounds 8, 10 and 15, were isolated for the first time from the Fissistigma species. All compounds were evaluated for their anti-inflammatory activities and anti-tumor activity. Compound 9 showed significant anti-inflammatory activity and inhibited the superoxide anion generation in human neutrophils by induced fMLP/CB. Compound 11 showed cytotoxicity against the human breast cancer cell lines MDA-MB-231.

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