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桦剥管菌和野山楂化学成分及生物活性研究
再娜布·吐合达洪
学位类型博士
导师袁涛
2017-06-03
学位授予单位中国科学院大学
学位授予地点北京
学位专业有机化学
关键词桦剥管菌 野山楂 羊毛甾烷型三萜 细胞毒性 生物活性
摘要

本论文对桦剥管菌(Piptoporus betulinus Bull.:Fr. Karst)和野山楂(Crataegus cuneata Sieb.&Zucc.)的化学成分和生物活性进行了系统研究。采用硅胶柱色谱、反向C-18硅胶柱色谱、Sephadex LH-20、MCI以及半制备液相色谱等多种色谱分离技术和UV、IR、NMR、HR-ESI-MS以及ECD等波谱学方法从上述生物样品中分离鉴定了33个化合物,并对所得到的部分单体化合物进行了生物活性研究。桦剥管菌(Piptoporus betulinus Bull.:Fr.Karst)为多孔菌科(Polyporaceae)剥管菌属(Piptoporus)大型真菌,又称桦滴孔菌、桦多孔菌,专门生长在桦木属(Betulina)的树干上。本论文对桦剥管菌化学成分进行了系统研究,从桦剥管菌甲醇提取物中分离得到了22个单体化合物(其中7个为新化合物)。所得到的新化合物都是羊毛甾烷型三萜类化合物: piptolinic acid A(HB-12),piptolinic acid B(HB-14),piptolinic acid C(HB-2),piptolinic acid D(HB-11),piptolinic acid E(HB-16),piptolinic acid F(HB-19),piptolinic acid G(HB-13);15个已知的化合物(包括13个羊毛甾烷型三萜,2个甾体):eburicoic acid ( HB-1),lup-20(29)-en-3α,28-doil (HB-3),ergota-5,7,22-trien-3?-ol ( HB-4 ),ergota-8,22-dien-3?-ol ( HB-5 ),polyporenic acid C ( HB-6 ),3-epi-dehydropachymic acid (HB-7),15α-acetoxy-3-oxo-24-methylenelanost-8-en-21-oic acid (HB-8),dehydropachymic acid(HB-9),lanost-8-en-21-oic acid(HB-10),6α-hydroxypolyporenic acid C(HB-15),3-epi-(3¢-hydroxy-3¢-methylglutaryloxyl)-dehydrotumulosic acid ( HB-17 ),fomefficinic acid F ( HB-18 ),3α,16α-dihydroxy-7-oxo-24-methyllanosta-8,24(31)-dien-21-oic acid( HB-20 ),3-epi-dehydrotumulosic acid ( HB-21 ),dehydrotumulosic acid ( HB-22 ) 。采用台盼蓝实验法对所得到的部分化合物(HB-2, HB-6, HB-7, HB-9, HB-11, HB-12, HB-13, HB-14, HB-15, HB-16)进行了抗HL-60(人类急性髓细胞性白血病细胞株)和THP-1(单核巨噬细胞)细胞毒性筛选,结果表明化合物HB-6,HB-15 和HB-17 对THP-1具有一定的细胞毒性(IC50 = 42.84~48.15 mM),而化合物HB-12表现出较强的细胞毒性( IC50 = 8.21 mM ),其他化合物对其未表现出细胞毒性(IC50 > 50 mM)。化合物HB-2,HB-9,HB-14和HB-15对HL-60有一定的细胞毒性( IC50 =18.28~42.32mM ),HB-12有很好的抑制作用(IC50 = 1.77 mM),而其他化合物对其未表现出细胞毒性( IC50>50 mM )。采用MTT 法对化合物HB-12进行了抗 PC-3 (人前列腺癌细胞株) 细胞毒性试验,实验结果表明化合物HB-12对PC-3具有很强的细胞毒性(IC50 = 9.77 mM)。野山楂(Crataegus cuneata Sieb.&Zucc.)为蔷薇科山楂属植物,习称南山楂。主要生于海拔250m-2000m米山谷或山地灌木丛中。民间验方及现代研究均表明其具有消食化积,止泻止痢,镇痛 ,抗癌,防菌,降压降脂等多种功效。本论文对野山楂化学成分进行了系统研究,从野山楂乙醇提取物中分离得到了11个单体化合物: lyoniresinol (YS-1) ,胡萝卜苷(YS-2) , lyoniresino-19-O-?-glucopyranoside (YS-3),epicatethin (YS-4),profisetinidin (YS-5),2α, 19α-dihydroxy-3-oxo-urs-12-en-28-oic acid (YS-6),pomolic acid (YS-7) ,ursolic acid (YS-8) ,euscaphic acid (YS-9) ,maslic alid (YS-10) ,corsolic acid (YS-11) ,其中化合物YS-7为首次从野山楂中分离得到, YS-8和YS-10首次从山楂属植物中分离得到。基于分离得到的大部分化合物为三萜类化合物,本论文优化了野山楂总三萜提取方法,并对所得到三萜类单体化合物以及总三萜提取物进行了乙酰胆碱酯酶,黄嘌呤酶和酪氨酸酶抑制活性评价,结果表明野山楂中得到的三萜类化合物YS-7,YS-8, YS-9 和 YS-10 有较弱的乙酰胆碱酯酶抑制活性(IC50=0.56~0.91mM),所有三萜化合物及总三萜提取物均表现出一定的黄嘌呤酶抑制活性(IC50=0.52~1.19 mM)以及酪氨酸酶抑制活性(IC50=0.76~1.35 mM)。

其他摘要

The present study mainly focused on the chemical constituents and biological activities of Piptoporus betulinus (Bull.: Fr. Karst) and wild hawthorn (Crataegus cuneata). 33 compounds were isolated and identification From Piptoporus betulinus and Crataegus cuneata by silica gel column chromatography, reverse C-18 column chromatography, Sephadex LH-20and MCI column chromatography and semi-preparative HPLC. Their structures were elucidated by the analysis of spectrospic data including UV, IR, NMR, HRESIMS. Moreover, some of the isolates were evaluated their biological activities.Piptoporus betulinus (Bull.: Fr.) Karst. (Polyporaceae), commonly known as the birch polypore, is an annual wood-rotting fungus on birch trunks and branches. In the current study, 22 compounds including seven new compounds were isolated from the methanolic extract of P. betulinus, seven new compounds were lanostane triterpenoids, named piptolinic acid A(HB-12), piptolinic acid B (HB-14), piptolinic acid C (HB-2), piptolinic acid D (HB-11), piptolinic acid E (HB-16), piptolinic acid F(HB-19), piptolinic acid G (HB-13); 14 known compounds were determined as eburicoic acid (HB-1), lup-20(29)-en-3α,28-doil (HB-3), ergota-5,7,22-trien-3?-ol (HB-4), ergota-8,22-dien-3?-ol (HB-5), polyporenic acid C (HB-6), 3-epi-dehydropachymic ( HB-7 ), 15a-acetoxy-3-oxo-24-methylenelanost-8-en-21-oic acid (HB-8 ), dehydropachymic acid ( HB-9 ), lanost-8-en-21-oic acid ( HB-10 ), 6α-hydroxypolyporenic acid C ( HB-15 ), 3-epi-(3¢-hydroxy-3¢-methylglutaryloxyl)-dehydrotumulosic acid ( HB-17 ), fomefficinic acid F ( HB-18 ), 3α,16α-dihydroxy-7-oxo-24-methyllanosta-8,24(31)-dien-21-oic acid( HB-20 ), 3-epi-dehydrotumulosic acid ( HB-21 ), dehydrotumulosic acid ( HB-22 ).Some of the isolates were tested for their cytotoxicity effects against human promyelocytic leukemia cell line HL-60 and human acute monocytic leukemia cell line THP-1 using the trypan blue method. Compounds HB-6, HB-15 and HB-17 showed weak cytotoxicity against THP-1 (IC50 = 42.84~48.15 mM), and compounds HB-2, HB-9, HB-14, and HB-15 exhibited weak cytotoxicity against HL-60 (IC50 = 18.28~42.32 mM), while compound HB-12 exhibited comparable cytotoxic activity against HL-60 (IC50=1.77 mM) and THP-1 (IC50= 8.21 mM) to those of positive control, fluorouracil (IC50 = 6.38 and 4.41 mM, respectively). Furthermore, MTT assay showed compound HB-12 showed strong cytotoxicity against PC-3 with IC50 value at IC50 = 9.77 mM.Crataegus cuneata Sieb. & Zucc. belongs to family Rosaceae, commonly known as wild hawthorn. It’s mainly distributed in the valley of 250 m-2000 m or mountain thickets. Folk prescription and modern studies show that it has several medicinal functions such as various digestive ailments, anti-diarrheal, analgesia, anti-cancer, anti-bacterial, anti-hypertensive. In the current study, 11 compounds were isolated from the Crataegus cuneata, their structures were identified as lyoniresinol (YS-1), carotene (YS-2), lyoniresino-19-O-?-glucopyranoside (YS-3), epicatethin (YS-4), profisetinidin (YS-5), 2α, 19α-dihydroxy-3-oxo-urs-12-en-28-oic acid (YS-6), pomolic acid (YS-7), ursolic acid (YS-8), euscaphic acid (YS-9), maslic acid (YS-10), corsolic acid (YS-11), Among them, YS-8 and YS-10 are being reported from the genus Crataegus for the first time, and compound YS-7 was firstly isolated from this species. Enzyme inhibition assays indicated that compounds YS-7, YS-8, YS-9 and YS-10 showed weak AChE inhibition (IC50 = 0.56~0.91 mM), while all of the triterpenoids exhibited considerable acitivties against XOD (IC50 = 0.52~1.19 mM) and tyrosinase (IC50 = 0.76~1.35 mM).

文献类型学位论文
条目标识符http://ir.xjipc.cas.cn/handle/365002/4973
专题资源化学研究室
作者单位中国科学院新疆理化技术研究所
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再娜布·吐合达洪. 桦剥管菌和野山楂化学成分及生物活性研究[D]. 北京. 中国科学院大学,2017.
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