海绵、福州薯蓣和齿叶黄杞的化学成分及其抗癌活性研究
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摘要
在从海洋生物中寻找海星卵母细胞成熟抑制活性成分的过程中(该模型被用来筛选G2/M细胞周期抑制剂),海绵(Phyllospongia dendyi)的乙醇提取物显示了较强的生物活性。利用多种分离手段从海绵(Phyllospongia dendyi)的乙醇提取物中分离得到11个化合物,其中2个新化合物,通过化学和光谱学方法,鉴定了它们的结构:2-(2', 4'-dibromophenoxy)-4, 6-dibromophenol (1), 2-(3',5'-dibromo-2'-methoxyphenoxy)-3, 5-dibromoanisole (2), 2-(4', 6'-dibromo-2'-methoxyphenoxy) -3, 5-dibromophenol (3), 2-(4', 5', 6'-tribromo-2'-methoxyphenoxy)-4, 6-dibromoanisole (4), 2-(3', 4', 6'-tribromo-2'-methoxyphenoxy)-4, 6- dibromophenol(5), 2-(3', 4', 5', 6'-tetrabromo-2'-methoxyphenoxy)-4, 6-dibromophenol (6)~*, 2-(4',6'-dibromo-2'-methoxyphenoxy)-4, 6-dibromophenol (7), 2-(4', 5', 6'-dibromo-2'-methoxyphenoxy)-4, 6-dibromophenol (8)~*, 2-(3', 4', 6'-tribromo-2'-hydroxyphenoxy)-4, 6-dibromophenol (9), 2-(4', 5', 6'-tribromo-2'-hydroxyphenoxy)-3,5-dibromophenol (10), 2-(3', 4', 5', 6'-tetrabromo-2'-hydroxyphenoxy)- 4, 6-dibromophenol(11),其中6、8是新化合物。
     对分离得到的多溴取代二苯醚类化合物进行了抗海星卵母细胞成熟活性(G2/M阻断活性)和抗微管蛋白聚集活性研究。研究发现,化合物9、10、11显示了较强的细胞周期抑制活性与微管蛋白聚集抑制活性。从试验结果推测,它们对海星卵母细胞成熟的抑制作用是源于它们对微管蛋白聚集的抑制作用。我们的研究首次揭示了溴取代二苯醚类化合物抑制海星卵母细胞成熟活性和抑制微管蛋白聚集活性,发现了一类新的微管蛋白抑制剂。它们的抗癌活性有待于进一步研究。
     作为对薯蓣科薯蓣属植物抗癌活性成分研究的一部分,我们利用稻瘟霉活性筛选(Pyricularia oryzae bioassay)模型对福州薯蓣(Dioscorea futschauensis Uline
     ex R. kunth)进行了生物活性成分的追踪分离及结构鉴定工作。利用现代色谱手段从福州薯蓣的根茎中分离得到28个化合物,其中7个为新化合物,通过化学
    
    沈阳称料大学俘创匕学位论文
    和光谱学方法,鉴定了它们的结构:p一谷幽醇(l),p一胡萝卜素(2),薯预皂昔
    元(3),DioseoroneA(4)*,3一phenyl一6,8一di场droxydihydroisoeoumarin(5)*,
    薯祯皂普元一3一O一p一D一毗喃葡萄糖普(6),薯预皂昔次级营A prosapogenin Aof
    diosein(7),薯预皂营次级普B pros即ogenin B ofdiosein(8),薯预皂营diosein(9),
    纤细皂普gracillin(10),(255卜spiros卜5、n一3p,27祖101一3一O一[a一L一rhamnopyranosyl
    (l分2)一p一D一glueoPyranosyl(1斗3)」一p一D一glueoPyranoside(dioseoresideF,11)*,
    26一O一p一D一glucoPyranosyl一3俘,26一ihydroxy一25(R)一furosta一5,20(22)一dien一3一O一a一L-
    rhamnopyranosyl(l分2卜p一D一glueopyranoside(12),伪原薯祯皂营pseudoProto
    diosein(13),伪原纤细皂普pseudoprotograeillin(14)*,dioseoresideC(15),26一O-
    p一D一glueoPyranosyl一3日,26甩i冲droxy一23(S)一methoxyl一25(R)一furosta一5,20(22)一dien
    一3一O一a一L一rhamnoPyranosyl(1分2)一[p一D一glueoPyranosyl(1分3)]一p一D-
    glucop”anoside(dioseoresideE,16)*,原薯预皂昔protodiosein(17),甲基原薯预
    皂昔methyl protodiosein(18),原新薯锁皂营protoneodiosein(19),甲基原新薯预
    皂昔methyl protoneodiosein(20),原纤细皂昔proto『acillin(21),甲基原纤细皂昔
    methyl protograeillin(22),原新纤细皂昔protoneograeillin(23),甲基原新纤细皂
    普methyl protoneograeillin(24),3p一[(0一a一L一rhamnopyranosyl一(l斗2)一O一[a一L-
    rhamnoPyranosyl一(1峥4)]一p一D一glueoPyranosyl)oxy]Pregn一5,16一en一20一one
    (h邓oglaueinF,25),3p一[(O一a一L一tharnnopyTanosyl一(1峥2)一O一[a一L一glucopyranosyl
    一(1分3)1一p一D一glueoPyranosyl)oxy]Pregn一5,16一en一20一one(26),16a一methoxyl一3p-
    [(O一a一L一rhamnoPyranosyl一(1分2)一O一汇a一L一rhamnoPyranosyl一(1峥4)]一p一D-
    9 lucopyranosyl)oxy]pregn一5一en一20一one(27)*,21一methoxyl一3p一「(O一a一L-
    tha们以nop皿anosyl一(1分2)一O一[a一L一thamnopyranosyl一(1分4)]一p一D一glueopyTanosyl)oxy]
    pregn一5,16一en一20一one(28)*。其中,化合物4、s、11、14、16、27和25为新化
    合物,全部4、5、7、8、11一28均为首次从该种植物中分离得到。
     利用招瘟霉活性筛选方法对从福州薯赣中芬禽得到的29个化合物进仔了居
    性测试,幽体皂普类成分显示了很强的抗稻瘟霉活性。在此基础上,利用MTT
    法测定了各单体化合物对K562细胞的细胞毒活性,部分幽体皂昔类化合物显示
    了较强的细胞毒活性。我们重点研究了化合物8(pros即ogenin B of diosein)对5
    种人体肿瘤细胞系的细胞毒活性和诱导HCT-巧细胞凋亡活性。结果表明,化合
    
    沈阳苟料大学俘d匕学位论文
    ?
In our continuous efforts on the screening of biologically active agents from sea, the ethanol extract of marine sponge Phyllospongia dendyi presented strong inhibitory bioactivity on the maturation of starfish oocyte Asterian pectinifera, an assay developed for the search of G2/M inhibitors. The bioassay-guided separation resulted in the isolation of 11 polybrominated diphenyl ethers. Their structures were established as ( new compounds were indicated with the asterisk.): 2-(2', 4'-dibromophenoxy)-4, 6-dibromophenol (1), 2-(3', 5'-dibromo-2'- methoxyphenoxy ) -3, 5-dibromoanisole (2), 2-(4', 6'-dibromo-2'-methoxyphenoxy)-3, 5-dibromophenol (3), 2-(4', 5', 6'-tribromo-2'-methoxyphenoxy)-4, 6-dibromoanisole (4), 2-(3', 4', 6'-tribromo-2'-methoxyphenoxy)-4, 6-dibromophenol (5), 2-(3', 4', 5', 6'-tetrabromo-2' -methoxyphenoxy)-4, 6-dibromophenol (6) *, 2-(4', 6'-dibromo-2'-methoxyphenoxy) -4, 6-dibromophenol (7), 2-(4', 5', 6'-dibromo-2'-methoxyphenoxy ) -4, 6-dibromo phenol (8) *, 2-(3', 4', 6'-tribromo-2'-hyd
    roxyphenoxy)-4, 6-dibromophenol (9), 2-(4', 5', 6'-tribromo-2'-hydroxyphenoxy)-3, 5-dibromophenol (10) , 2-(3', 4', 5', 6'-tetra bromo-2'-hydroxyphenoxy)-4, 6-dibromphenol(11) by NMR spectra analysis and comparison with the reference data.
    The G2/M cell cycle inhibitory activity of compounds 1-11 on first meiotic division of starfish oocytes was evaluated. Compounds 9, 10, and 11 showed inhibitory activity on meiotic maturation of starfish oocytes (G2/M arrest) with the IC50 value of 4.2, 4.2, and 3.6 uM, the integrate germinal vesicles were observed under microscope. On the same time, compounds 9, 10 and 11 presented a promising inhibitory activity on microtubulin polymerization in vitro. IC50 value was determined
    as 33.5, 20.9, and 29.6 uM, respectively. It seems that compounds 9, 10, and 11 inhibit the maturation of starfish oocytes via the inhibition of microtubulin polymerization. It is the first report of above-mentioned biological activities for the polybrominated diphenyl ethers. Based on the above bioactivities study, the structure-activity relationship information was obtained.
    As a part of our continuous study on the anti-cancer components from plants of
    
    
    Dioscorea genus, the ethanol extract of Dioscorea futschauensis Uline ex R. Kunth was under bioassay-guided isolation, using a Pyricularia oryzae bioassay. 28 compounds were isolated from the n-butanol soluble fraction. Their structures were elucidated on the basis of physico-chemical and NMR spectral methods as (new compounds were indicated with asterisk.): p-sitosterol (1), p-daucosterone(2), diogenin(3), Dioscorone A (4)*, 3-phenyl-6, 8-dihydroxydihydroisocoumarin(5)*, diosgenin-3-O-(3-D-glucopyranoside(6), prosapogenin A of dioscin(7), prosapogenin B of dioscin(8), dioscin (9), gracillin (10), (25S)-spirost-5-en-3p, 27-diol-3-O-[a-L-rhamnopyranosyl(1-2)-B-D-glucopyranosyl(1-3)]-B-D-glucopyranoside (dioscoreside F, 11)*, 26-O-B-D-glucopyranosyl-3p, 26-dihydroxy-25 (R)-furosta-5, 20(22)-dien-3-O-a-L-rhamnopyranosyl(1-2)-p-D-glucopyranoside (12), pseudoprotodioscin (13), pseudoprotogracillin (14) *, dioscoreside C (15), 26-Op-D-glucopyranosyl-3p, 26-dmydroxy-23(S)-methoxyl-25(R)-furosta-5, 20(22)-dien-3-O-a-L-rhamnopyranosyl (1-2)-[p-D-glucopyranosyl(1-3)]-B-D-glucopyranoside (dioscoreside E, 16)*, protodioscin (17), methyl protodioscin (18), protoneodioscin (19), methyl protoneodioscin (20), protogracillin (21), methyl protogracillin (22), protoneogracillin (23), methyl protoneogracillin (24), 3p- [(O-a-L-rhamnopyranosyl -(1-2)-O-[a-L-rhamnopyranosyl-(1-4)]-B-D-glucopyranosyl)oxy]pregn-5, 16-en-20-one(hypoglaucin F, 25), 3B-[(O-a-L-rhamnopyranosyl-(1-2)-O-[a-L-glucopyranosyl-(1-3)]-B-D-glucopyranosyl)oxy]pregn-5, 16-en-20-one (26), 16a-methoxyl-3p-[(O-a-L-rhamnopyranosyl-(1-2)-O-[a-L- rhamnopyranosyl-(1-4)]-B-D-glucopyrano syl)oxy]pregn-5-en-20-one (27) * , 21-methoxyl-3B-[(O-a-L-rhamnopyranosyl-(1-2)-O-[a-L-rhamnopyranoyl-(1-4)]-B-D-glucopyranosyl) oxy]pregn-5,16-en-20-one (28) *.
    The anti-fungal activity and cytotoxicity on K562 ce
引文
1. Rocha A.B.,Lopes R.M.,Schwantsmann G.,Natural products in anticancer therapy,Current Opinion in Pharmacology,2002,1,364-369
    2.郭跃伟,欧洲海洋药物的研究现状及对我国海洋药物研究的启示(2000上海科技论坛)
    3.郭跃伟,海洋天然产物的应用前景展望,中国海洋药物,200,19(2),
    4. Faulkner D.J., Highlights of marine natural products chemistry, Nat. Prod Rep., 2000, 17,1-6
    5. Munro M.H.G., Blunt J.H., Dumdei E.J., et al., The discovery and development of marine compounds with pharmaceutical potential, Journal of Biotechnology, 1999, 70, 15-25.
    6. Carte B., Faulkner D, J., Polybrominated diphenyl ethers from Dysider herbacea, Dysidea chlorea and Phyllospongia foliascens, Tetrahedron, 1981, 37, 2335-2339
    7. Fu X., Schmitz, F.J., Govindan M., Abbas S.A., Enzyme inhibitors: new and known polybrominated phenols and diphenyl ethers from four indo-pacific Dysidea sponge, J. Nat. Prod., 1995, 58(9), 1384-1391.
    8. Utkina N.K., Denisenko V.A., Scholokova O.V., et al., Spongiadioxins A and B, two new polybrominated dibenzo-p-dioxins from an Australian marine sponge Dysidea dendyi, J. Nat. Prod, 2001, 64, 151-153.
    9. Hattori T., Konno A., Adachi K., Shizuri Y., Four new bioactive bromophenols from the Palauan sponge Phyllospongia dendyi, Fisheries Scinece, 2002, 67, 899-903
    10. Hu, k., Dong, A. J., Yao, X. S., Et al., Antineoplastic Angents Ⅱ. Four Furostanol Glycosides from Rhizomes of Dioscorea collettii var. hypoglauca, Planta Med., 1997, 63, 161-165
    11. Hu, k., Dong, A. J., Yao, X. S., Et al., A Furostanol Glycoside from Dioscorea collettii var. hypolauca, Phytochemistry, 1997, 44(7), 1339-1342
    12. Hu, k., Dong, A. J., Yao, X. S., Et al., Antineoplastic Steroidal Saponins from
    
    Rhizomes of Dioscorea collettii var. hypoglauca, Stud Plant Sci., 1999, 6 (Advances in Plant Glycosides, Chemistry and Biology), 220-229
    13. Dong, M., Chen, Q., Wu, L. J., Et al., Chemical constituents of Dioscorea panthaica (Ⅱ), Zhangcaoyao, 2001, 32(8), 685-686
    14. Dong, M., Feng, X. Z., Wang, B. X., Et al., Two novel furostanol saponins from the rhizomes of Dioscorea panthaica Prain et Burkill and their cytotoxic activity, Tetrahedron, 2001, 57(3), 501-506
    15. Li, B. G., Tang, Y. F., Shi, Y., Isolation and identification of steroidal saponins from Dioscorea panthaica Prain et Burkill, Zhiwu Xuebao, 1986, 28(4), 453-456
    16. Liu, H. W., Kobayashi, H., Qu, G. X., Et al, A new spirostanol saponin from Dioscorea futshauensis, Chin. Chem. Lett., 2001, 12(7), 613-616
    17. Liu, C. L., Chen, Y. Y., Chemical constituents of Dioscorea plants Ⅷ. Isolation and identification of steroidal saponins and sapogenins from Foochow yam(Dioscoreafutschauensis), Zhongcaoyao, 1984, 15(9), 10-12
    18. Hu, k., Yao, X. S., Methyl protogracillin (NSC-698792): the spectrum of cytotoxicty against 60 human cancer cell lines in the National Cancer Institute's anticancer drug screen panel, Anti-Cancer Drugs, 2001, 12(6), 541-547
    19. Tang, S. R., Jiang, Z. D., Pang, Z. J., Isolation and identification of steroidal saponins of Dioscorea collettii Hook. var. hypoglauca (Paiibin) Pei et Ting (Ⅱ), Zhiwu Xuebao, 1986, 28(4), 453-456
    20. Haraguchi, M., Young, M. C. M., Chu, D. P., Et al, Chemical constituents from Dioscorea delicata, Brazil. Nat. Med., 1999, 53(2), 110
    21. Mustafa, A. M., Mohamed, X., Akaria, M. B., Piscatorim, a new saponin from Dioscorea piscatorum, Proc. Malays. Biochem. Soc. Conf , 1994, 19th, 266-269
    22. Son, K. H., Jung, K. Y., Do, J. C., Saponin constitutes from the rhizomes of Dioscorea quinqueloba, Saengyak Hakhoechi, 1993, 24(3), 187-189
    23. Tang, S. R., Jiang, Z. D., Three new steroidal saponins from the aerial part of Dioscorea zingiberensis, Yunnan Zhiwu Yanjiu, 1987, 9(2), 233-238
    24. Liu, C. L., Chen, Y. Y., Tang, Y. F., Isolation and identification of steroidal saponins from Dioscorea zingiberensis Wright, Zhiwu Xuebao, 1984, 26(3),
    
    283-289
    25. Tang, S. R., Wu, Y. F., Pang, Z. J., Identification and isolation of steroidal of Dioscorea zingiberensis Wright, Zhiwu Xuebao, 1983, 25(6), 556-562
    26. Nguyen, X. C., Zeigan, D., Voigt, G., Hiller, k., Seroidal saponins of Dioscorea hispida L., Pharmazie, 1987, 42(2), 143
    27. Dong, V. T., Nguyen, V. D., Nguyen, T. D., Study of Dioscorea deltoidea Wall. grown in Vietnam. Ⅲ. The main spirostan-saponins in the rhizome, Rev. Pharm.(1985), 20-27
    28. Paseshnichenko, V. A., Guseva, A. R., Strigina, L. I., Et al, Structure of deltofolin-a steroidal saponin from leaves of Dioscorea deltoidea Wall, Dokl. Akad Nauk SSSR, 1981, 256(3), 742-745
    29. Tang, S. R., Jiang, Z. D., Steroidal saponins of Dioscorea tokoro Makino(collected from Zhejiang), Zhiwu Xuebao, 1987, 29(2), 193-196
    30. Uomori, A., Seo, S., Tori, A., Et al, Protoyonogenin and Protoneoyonogenin from the aerial parts and tissue cultures of Dioscorea tokoro, Phytochemistry, 1983,22(1), 203-206
    31. Liu, C. L., Chen, Y. Y., Ge, S. B., Isolation and identification of steroidal saponins from Dioscorea parviflora Ting, Zhiwu Xuebao, 1985, 27(6), 635-639
    32. Tang, S. R., Wu, Y. F., Isolation and identification of steroidal saponin from Dioscorea gracillima Miq., Zhiwu Xuebao, 1984, 26(6), 630-633
    33. Liu, C. L., Chen, Y. Y., Studies on chemical constituents of Dioscorea plants. Ⅹ. Isolation and identification of steroidal saponins and sapogenins from Dioscorea althaeoides Kunth, Yaoxue Xuebao, 1984, 19(10), 799-801
    34. Liu, C. L., Chen, Y. Y., Ge, S. B., Studies on the chemical constituents of Dioscorea plants. Ⅱ. Isolation and identification of steroidal saponins from Dioscorea collettii Hook. f., Yaoxue Xuebao, 1983, 18(8), 597-606
    35. Kalogjera, Z., Petricic, J., Cultivated plant Dioscorea nipponica Thunb. Raw material for the isolation of diosgenin (basic substance for the synthesis of corticosteroids), Farm. Vestn. (Ljubljana), 1983, 34(2), 71-75
    36. Fang, Y. W., Zhao, J. J., Ho, Y. Z., Et al, Elucidation of the chemical structures of
    
    two steroid saponins of Dioscorea nipponica Makino, Yaoxue Xuebao, 1982,17(5), 388-91
    37. Espejo, O., Llavot, J. C., Jung, h. Giral, F., Spirostanic diosgenin precursors from Dioscorea composita tubers, Phytochemistry, 1982, 21 (2), 413-416
    38. Mahato, S. B., Sahu, N. P., Ganguly, A. N., Steroidal saponin from Dioscorea floribunda: structures of floribundasaponins A and B, Phytochemistry, 1981,20(8), 1943-1946
    39. Mhato, S. B., Sahu, N. P., Pal, B. C., New steroidal saponins from Dioscorea floribunda: structures of floribundasaponins C, D, E, and F, Indian J. Chem., Sect. B, 1978, 16B(5), 350-354
    40. Hoyer, G. A., Sucrow, W., Winkler, D., Diosgenin saponins from Dioscorea floribunda, Phytochemistry, 1975, 14(2), 539-542
    41. Joly, R. A., Bonner, j., Bennett, R. D., Et al, Conversion of an open-chain saponin to dioscin by a Dioscorea floribunda homogenate, Phytochemistry, 1969, 8(8), 1445-1447
    42. Kiyosawa, S., Goto, K., Sakamoto, K., Et al, A spirostanol glycoside from aerial parts of Dioscorea tenuipes, Phytochemistry, 1982, 21(12), 2913-2915
    43. Kiyosawa, S., Goto, K., Owashi, R., Et al, Glycosides of 20,22-seco-furostane detrivatives, Tetrahedron Lett., 1977, 52, 4599-4602
    44. Kawasaki, T., Yamauchi, T., Yamauchi, R., Saponins of Japanese dioscoreaceae.Ⅹ. Ⅺ. Kikuba saponin. 1.2, Chem. Pharm. Bull., 1962, 10, 698-702, 703,708
    45. Paseshnicahenkko, V. A., Vasil'eva, I. S., Guseva, A. R., Steroid saponins from leaves of the Caucasian Chinese yam Dioscorea caucasica Lipsky, Prikl. Biokhim. Mikrobiol., 1982, 18(2), 171-173
    46. Hraguchi, M., Santos, A.P.Z.D.,Young, M.C.M., Et al, Steroidal prosapogenins from dioscorea olferslana, Phytochemistry, 1994, 36(4), 1005-1008
    47. Sokolova, 1. N., Effects of the saponins of a Dioscorea and blue cornflower(Polemonium caeruleum) on the development of experimental atherosclerosis in rabbits, Lekarstv. Sredstva iz Rast. 1962, 113-31
    
    
    48.江苏新医学院编,中药大辞典,上海,上海人民出版社,1977
    49. Chou, J., Wu, T. K., Huang, W. K., The saponin components of plants in Yunnan.Ⅱ. Steroid sapogenin of Dioscoreaceae and Agavaceae, Yao Hsueh Hsueh Pao,1965, 12(6), 392-398
    50.中国植物志编委会.中国植物志[M](第二十七卷).北京:科学出版社,1979.11-18.
    51.福建中医研究所.福建药物志[M](第二卷).福建:福建科技出版社,1983.69.
    52. Yoshida, N., Mita, K., Yamashita M., Comparative study of the molecular mechanism of oocyte maturation in amphibians, Comparative Biochemistry and Physiology Part B, 2000, 126, 189-197.
    53. Kanatani, H., Shirai, H., Nakanishi, K., Kurokawa, T., Isolation and identification of meiosis-inducing substance in starfish, Asterias amurensis. Nature, 1969, 221,273-274.
    54. Morinaga, C., Izumi, K., Sawada, H., Sawada, M. T., Activation of maturation promoting factor and 26S proteasome assembly accelerated by a high concentration of 1-methyladenine in starfish oocytes., Biosci. Biotechnol. Biochem, 2000, 64, 268-274.
    55. Kanatani, H. Hormones in echinoderm. Hormones and evolution, vol. 1; Academic Press: New York, 1979.
    56. Kishimoto, T., Kanatani, H., Cytoplasmic factor responsible for gonad vesicle breakdown and meiotic maturation in starfish oocyte, Nature, 1976, 260, 321-322.
    57. Dunphy, W. G., Brizuela, L., Beach, D., Newport, J., The xenopus cdc2 protein is a component of MPF, a cytoplasmic factor from Xenopus.,Cell, 1988, 54, 423-431.
    58. Gautier, J., Minshull, J., Lohka, M. Glotzer, M. et al., Cyclin is a component of maturation-promoting factor from Xenopus. Cell, 1990, 60, 487-494.
    59. Gautier, J., Norbury, C., Lohka, M., Nurse, P., et al., Purification
    
    maturation-promoting factor contains the product of a Xenopus homolog of the fission yeast cell cycle control gene cdc,. Cell, 1988, 54, 433-439.
    60. Yoshikuni, M., Ishikawa, K., Isobe, M., Goto, T., Nagahama, Y., Characterization of 1-methyl adenine binging in starfish oocyte cortices, Proc. Natl. Acad. Sci., USA. 1988, 85, 1874-1877.
    61. Toraya, T.; Maoka, T.; Tsuji, H.; Kobayashi, M. Purification and structural determination of an inhibitor of starfish oocyte maturation from a Bacilus speciese., Applied and Environ. Micro., 1995, 61, 1799-1804
    62. Ngales, E.; Wolf, S.G ,Downing H.K.,Structure of the αβ tubulin dimer by electron crystallography. Nature 1998, 391. 199~203.
    63. Jordan, M. A., Wilson, L., Microtubules and actin filaments: dynamic targets for cancer chemotherapy. Curt. Opin. Cell Biol. 1998, 10, 123~130.
    64. Andersen, S.S.L., Balanced regulation of microtubule dynamics during the cell cycle: a contemporary view. BioEssays, 1999, 21, 53~60.
    65. Meguro, S., Namikoshi, M., Kobayashi, H., A new screening method for antimitotic substances and isolation of glyeolipids as stimulators of tubulin polymerization from Okinawan sponge Pseudoceratina sp. J Antibiotics, 2002, 55(3), 256-262.
    66. Mosmann T., Rapid colorimetrie assay for cellular growth and survival: application to proliferation and cytotoxicity assay, J. Immunol. Meth. 1993, 13, 711-719
    67.小林久芳,具有微管机能阻碍作用的微生物代谢产物的研究 (日本东京大学,博士论文,1997)
    68. Takahashi, M., Iwasaki, S., Kobayashi, H., Et al., Studies on Macrocyclic Lacton Antibiotics Ⅺ, Antimitotic and Anti-tubulin Activity of new Antitumor Antibiotics, Rhizoxins andits Homologues, J. Antibiotics, 1987, 40, 66-72
    69. Kobayashi, H., Namikoshi, M., Yoshimoto, T., Et al., a screening Method ofr Antimitotic application to Tropical Marine Fungi, J. Antibiotics, 1996, 49(9),
    
    873-879
    70. Kobayashi, H., Sunaga, G., Furihara, K., Et al., Isolation and Structures of an Antifungal Antibiotic fusarielin A, and Related Compounds Produced by a Fusarium sp, J. Antibiotics, 1995, 48, 42-52.
    71. Majumder, P. L., Banerjee, S., Sen, S., Three stilbenoids from the orchid Agrostophyllum callosum, Phytochemistry, 1996, 42, 847-852.
    72. Majumder, P.L., Lahiri, S., Mukhoti, N., Four stilbenoids from the orchid Agrostophyllum khasiyanum, Phytochemistry, 1996, 42, 1157-1161.
    73. Yoshikawa, M., Matsuda, H., Shimoda, H., et al., Development of bioactive functions in Hydrangeae dulcis folium. V. on the antiallergic and antimicrobial principles of Hydrangeae dulcis folium. (2). Thunbergionols C, D, and E, Thunberginol G 3'-O-glucoside, (-)-hydrangenol 4"-O-glucoside, and (+)-hydrangenol 4"-O-glucoside, Chem. Pharm. Bull. 1996, 44, 1440-1447.
    74. Blunden, G., Patel, A. V., Brabourgenin, A new steroidal sapogenin from Agave sisalana leaves, J. Nat. Prod., 1986, 49(4), 687-689.
    75. Agrawal, P. K., Jain, D.C., Gupta, P.K., Thakur, R.S., Carbon-13 NMR spectroscopy of steroidal sapogenins and steroidal saponins, Phytochemistry, 1985, 24, 2479-2485.
    76. Dong, M., Feng, X.Z., Wu, L.J., Wang, B.X., Ikejima, T., Two new steroidal saponins from the rhizomes of Dioscorea panthaica and their cytotoxic activity, Planta Med., 2001, 67, 853-857.
    77. Dong, M., Wu, L.J., Chen, Q., Wang, B.X., Isolation and identification of steroidal saponins from Dioscorea panthaica Prain et Burkill, Acta Pharmaceutica Sinica. 2001, 36, 42-45.
    78. Terada, S., Hayashi, K., Mitsuhoshi, H., On the structure of stephanthraniline C., Tetrahedron Lett., 1978, 23, 1995-1998.
    
    
    79.董爱军,菊叶薯蓣活性成分研究(沈阳药科大学硕士论文,2000)
    80.胡柯,三种抗癌中草药的活性成分研究(沈阳药科大学博士论文,1998)
    81. Espejo, O., Llavot, J. C., Jung, H., Et al, Spirostanic diosgenin precursors from Dioscorea composita tubers, Phytochemistry, 1982, 21(2), 413-416。
    82. San, A. T., Betrand, R., Distinct steps in DNA fragmentation pathway during camptothecin-induced apoptosis involved caspase-, bezyloxycarbonyl- and N-tosyl-L-phenylalanylchloromethyl ketone-sensitive activities., Cancer Research, 1998, 58, 3066-3072.
    83. Wang, D.W., Li, F.M., Jiang, Z.H., Osteoblastic proliferation stimulating activity of Psoralea corylifolia extracts and two of its flavonoids. Planta Med, 2002, 67,748-749.
    84. Oda, T., So, Y., Sato, Y., et al. Inhibition by (±)-indenestrol A of interferon gamma-stimulated nitric oxide formation in murine macrophage RAW 264.7 cell., Mutation Research, 2003, 534, 187-195.
    85. Li, T.S., Jiang, Z.H., Mu, Z.B., Zhou, R.H., The ether constituents from the bark of Engelhardtia fenzeli Merr. Journal of Plant Resources and Environment, 1993,2(1), 7-9.
    86. Mu, Q., Li, C., Sun, H. Chemical constituents of Coleus carnosifolius Dunn., 中国中药杂志, 1996,21,104-110.
    87. Huang, H., Zhao, S., Wang, M., Liu, Q., Sun, H., Chemical constituents in the stem and leaf of Isodon oresbius, 中国中药杂志, 1998, 23, 37-38.
    88.陈连剑.猴耳环中某些酸性成分的分离与鉴定,广东医学院学报,1994,12(1):40-41.
    89. Kenji Tsujuhara,Mitsuya Hongu,Kunio Saito, et al.Na~+-Glucose cotransporter inhibiors as antidiabetics. Synthesis and pharmacological properties of 4'-dehydrophlorizinderivatives based on a new concept., Chem Pharm Bull,1996,44(6): 1174-1180
    90.姚新生,赵守训,潘德济等.天然药物化学[M]第二版.北京:人民卫生出版社,1992.247
    91. Kanojia, R.M., Ohemeng, K.A., Schwender, C.F., Barrett, J.F., Synthesis of the
    
    diaza analogue of ellagic acid., Tetrahedron Lett., 1995, 36(47), 8553-8556.
    92. Liu, X.Q., Jia, Z.J., Liu, Z.M., Studies on the components of Sanguisorba officinalis L. Chemical Journal of Chinese University, 1992, 13,767-769.
    93. Kwon, H. J., Shim, J. S., Kim, J.H., et al., Betulinic acid inhibitors growth factor-induced in vitro angiogenesis via the modulation of mitochondrial function in endothelial cells, JPN J Cancer Res., 2002, 93(4), 417-425.
    94. Zuco, V., Supino, R., Righetti, S.C., et al. Selective cytotoxicity of betulinic acid on tumor cell lines, but not on normal cells., Cancer Lett., 2002, 175(1), 17-25.
    95. Fulda, S., Debatin K.M., Betulinic acid induces apoptosis through a direct effect on mitochondria in neuroectodermal tumors., Med Pediatr Oncol., 2000, 35(6), 616-618.
    96. Fulda, S., Jeremias, I., Steiner, H.H., et al., Betulinic acid: a new cytotoxic agent against malignant brain-tumor cells., Int J Cancer, 1999, 82(3), 435-441.
    97. Huang, J., Sun, Y., Lu, S., Experimental study on apoptosis induced by ursolic acid isolated from asparagus in HL-60 cells., 中国中西医结合杂志, 1999,19(5), 296-298.
    98. Novotny, L., Vachalkova, A., Biggs, D., Ursolic acid: an anti-tumorigenic and chemopreventive activity., Neoplasma, 2002, 48(4), 241-246.
    99. Hollosy, F., Meszaros, G.., Bokonyi, G., et al., Cytostatic, cytotoxic and protein tyrosine kinase inhibitory activity of ursolic acid in A431 human tumor cell., Anticancer Res., 2000, 20(6B), 4563-4570.
    100. Kashiwada, Y., Nagao, T., Hashimoto, A., et al., Anti-aids agents 38: Anti-HIV activity of 3-O-acyl ursolic acid derivatives., J Nat Prod, 2000, 63(12), 1619-1622.

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