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    題名: Coumarin衍生物的抗氧化作用之活性探討
    作者: 周裕翔
    貢獻者: 醫學科學研究所
    日期: 2010
    上傳時間: 2010-08-31 10:44:02 (UTC+8)
    摘要: 在之前的研究中我們確定了baicalein會刺激B16F10小鼠黑色素瘤細胞株產生superoxide及hydroxyl radical,且認為此reactive oxygen species (ROS)的生成過程與arachidonic acid (AA)的代謝路徑有關,同時baicalein也造成了細胞存活率下降和細胞凋亡。本次研究我們用electron spin resonance (ESR)直接分析不同的系統,來偵測coumarin 衍生物的抗氧化活性。第一個系統是使用DPPH,分析結果發現各種coumarin 衍生物皆有抗氧化的活性;第二個系統是xanthine oxidase / hypoxanthine系統,直接偵測superoxide的強度,結果發現各種coumarin 衍生物也都有抗氧化的活性;第三個系統是直接分析B16F10老鼠黑色素瘤腫瘤細胞受到baicalein刺激後所釋放之hydroxyl radical,結果發現在coumarin 衍生物中的Mei-174、Mei-215、Mei-228、Mei-234也有抗氧化的活性。我們也使用MTT assay來觀察其對於B16F10小鼠黑色素瘤細胞是否可以減少baicalein所造成的細胞存活率下降,結果發現給予各種coumarin 衍生物皆沒有明顯的影響。各種coumarin 衍生物在不同系統的抗氧化程度可供日後繼續探討其機轉的參考。

    In our previous study, we demonstrated that baicalein induced superoxide and hydroxyl radical formation in B16F10 mouse melanoma cell line. We also found the reactive oxygen species (ROS) production is related to the arachidonic acid (AA) metabolism way. Simultaneously baicalein caused reduction of cellular viability and cell apoptosis. In this study, we use electron spin resonance (ESR) to analyze different systems, investigating the antioxidant activity of coumarin derivatives. System I using DPPH and found that coumarin derivatives all have the antioxidant activity. System II is xanthine oxidase / hypoxanthine system, directly investigating the superoxide intensity, and we found that coumarin derivatives also all have the antioxidant activity. System III directly analyze baicalein induced hydroxyl radical formation in B16F10 mouse melanoma, we found that coumarin derivatives Mei-174、Mei-215、Mei-228 and Mei-234 have the antioxidant activity. We also use coumarin derivatives to observe whether they can reduce the reduction of cellular viability effect to baicalein in B16F10 cell by MTT assay, the data show that coumarin derivatives have no obvious effect on cellular
    4
    viability. The antioxidant activity of coumarin derivatives in different systems can refer to the future study of their mechanism.
    關聯: 57頁
    描述: 中文摘要…………………………………………… 2
    英文摘要…………………………………………… 3
    縮寫表……………………………………………… 5
    壹、緒論…………………………………………… 6
    貳、材料與方法
    實驗材料……………………………………… 19
    實驗方法……………………………………… 23
    参、結果…………………………………………… 27
    肆、討論…………………………………………… 30
    伍、結論與展望…………………………………… 34
    陸、附圖…………………………………………… 35
    柒、圖表…………………………………………… 37
    捌、參考文獻……………………………………… 47

    Abe, R., Fujita, Y. & Yamagishi, S. 2007. Angiogenesis and metastasis inhibitors for the treatment of malignant melanoma. Mini Rev Med Chem 7: 649-61.
    Appendino, G., Mercalli, E., Fuzzati, N., Arnoldi, L., Stavri, M., Gibbons, S., Ballero, M. & Maxia, A. 2004. Antimycobacterial coumarins from the sardinian giant fennel (Ferula communis). J Nat Prod 67: 2108-10.
    Babior, B. M. 2000. The NADPH oxidase of endothelial cells. IUBMB Life 50: 267-9.
    Baldi, A., Lombardi, D., Russo, P., Palescandolo, E., De Luca, A., Santini, D., Baldi, F., Rossiello, L., Dell'Anna, M. L., Mastrofrancesco, A., Maresca, V., Flori, E., Natali, P. G., Picardo, M. & Paggi, M. G. 2005. Ferritin contributes to melanoma progression by modulating cell growth and sensitivity to oxidative stress. Clin Cancer Res 11: 3175-83.
    Bedogni, B., Welford, S. M., Cassarino, D. S., Nickoloff, B. J., Giaccia, A. J. & Powell, M. B. 2005. The hypoxic microenvironment of the skin contributes to Akt-mediated melanocyte transformation. Cancer Cell 8: 443-54.
    Bedoya, L. M., Beltran, M., Sancho, R., Olmedo, D. A., Sanchez-Palomino, S., del Olmo, E., Lopez-Perez, J. L., Munoz, E., San Feliciano, A. & Alcami, J. 2005. 4-Phenylcoumarins as HIV transcription inhibitors. Bioorg Med Chem Lett 15: 4447-50.
    Chang, W. S. & Chiang, H. C. 1995. Structure-activity relationship of
    48
    coumarins in xanthine oxidase inhibition. Anticancer Res 15: 1969-73.
    Chen, X., Wang, S., Wu, N., Sood, S., Wang, P., Jin, Z., Beer, D. G., Giordano, T. J., Lin, Y., Shih, W. C., Lubet, R. A. & Yang, C. S. 2004. Overexpression of 5-lipoxygenase in rat and human esophageal adenocarcinoma and inhibitory effects of zileuton and celecoxib on carcinogenesis. Clin Cancer Res 10: 6703-9.
    Chou, D. S., Hsiao, G., Lai, Y. A., Tsai, Y. J. & Sheu, J. R. 2009. Baicalein induces proliferation inhibition in B16F10 melanoma cells by generating reactive oxygen species via 12-lipoxygenase. Free Radic Biol Med 46: 1197-203.
    Chou, D. S., Hsiao, G., Shen, M. Y., Tsai, Y. J., Chen, T. F. & Sheu, J. R. 2005. ESR spin trapping of a carbon-centered free radical from agonist-stimulated human platelets. Free Radic Biol Med 39: 237-48.
    Egan, D., O'Kennedy, R., Moran, E., Cox, D., Prosser, E. & Thornes, R. D. 1990. The pharmacology, metabolism, analysis, and applications of coumarin and coumarin-related compounds. Drug Metab Rev 22: 503-29.
    Farombi, E. O. & Fakoya, A. 2005. Free radical scavenging and antigenotoxic activities of natural phenolic compounds in dried flowers of Hibiscus sabdariffa L. Mol Nutr Food Res 49: 1120-8.
    Ferrari, A. M., Sgobba, M., Gamberini, M. C. & Rastelli, G. 2007. Relationship between quantum-chemical descriptors of proton dissociation and experimental acidity constants of various hydroxylated coumarins. Identification of the biologically active species for xanthine oxidase inhibition. Eur J Med Chem 42: 1028-31.
    Finkel, T. 2001. Reactive oxygen species and signal transduction. IUBMB
    49
    Life 52: 3-6.
    Finkelstein, E., Rosen, G. M., Rauckman, E. J. & Paxton, J. 1979. Spin trapping of superoxide. Mol Pharmacol 16: 676-85.
    Forman, H. J. & Torres, M. 2002. Reactive oxygen species and cell signaling: respiratory burst in macrophage signaling. Am J Respir Crit Care Med 166: S4-8.
    Fruehauf, J. P. & Meyskens, F. L., Jr. 2007. Reactive oxygen species: a breath of life or death? Clin Cancer Res 13: 789-94.
    Fujita, M., Shiota, S., Kuroda, T., Hatano, T., Yoshida, T., Mizushima, T. & Tsuchiya, T. 2005. Remarkable synergies between baicalein and tetracycline, and baicalein and beta-lactams against methicillin-resistant Staphylococcus aureus. Microbiol Immunol 49: 391-6.
    Fylaktakidou, K. C., Hadjipavlou-Litina, D. J., Litinas, K. E. & Nicolaides, D. N. 2004. Natural and synthetic coumarin derivatives with anti-inflammatory/ antioxidant activities. Curr Pharm Des 10: 3813-33.
    Gaggioli, C. & Sahai, E. 2007. Melanoma invasion - current knowledge and future directions. Pigment Cell Res 20: 161-72.
    Galm, U., Dessoy, M. A., Schmidt, J., Wessjohann, L. A. & Heide, L. 2004. In vitro and in vivo production of new aminocoumarins by a combined biochemical, genetic, and synthetic approach. Chem Biol 11: 173-83.
    Ghate, M., Kusanur, R. A. & Kulkarni, M. V. 2005. Synthesis and in vivo analgesic and anti-inflammatory activity of some bi heterocyclic coumarin derivatives. Eur J Med Chem 40: 882-7.
    Ghate, M., Manohar, D., Kulkarni, V., Shobha, R. & Kattimani, S. Y. 2003.
    50
    Synthesis of vanillin ethers from 4-(bromomethyl) coumarins as anti-inflammatory agents. Eur J Med Chem 38: 297-302.
    Govindarajan, B., Sligh, J. E., Vincent, B. J., Li, M., Canter, J. A., Nickoloff, B. J., Rodenburg, R. J., Smeitink, J. A., Oberley, L., Zhang, Y., Slingerland, J., Arnold, R. S., Lambeth, J. D., Cohen, C., Hilenski, L., Griendling, K., Martinez-Diez, M., Cuezva, J. M. & Arbiser, J. L. 2007. Overexpression of Akt converts radial growth melanoma to vertical growth melanoma. J Clin Invest 117: 719-29.
    Hendrix, M. J., Seftor, E. A., Hess, A. R. & Seftor, R. E. 2003. Vasculogenic mimicry and tumour-cell plasticity: lessons from melanoma. Nat Rev Cancer 3: 411-21.
    Hess, A. R., Seftor, E. A., Seftor, R. E. & Hendrix, M. J. 2003. Phosphoinositide 3-kinase regulates membrane Type 1-matrix metalloproteinase (MMP) and MMP-2 activity during melanoma cell vasculogenic mimicry. Cancer Res 63: 4757-62.
    Hoult, J. R. & Paya, M. 1996. Pharmacological and biochemical actions of simple coumarins: natural products with therapeutic potential. Gen Pharmacol 27: 713-22.
    Hsu, S. L., Hsieh, Y. C., Hsieh, W. C. & Chou, C. J. 2001. Baicalein induces a dual growth arrest by modulating multiple cell cycle regulatory molecules. Eur J Pharmacol 425: 165-71.
    Huang, H. C., Wang, H. R. & Hsieh, L. M. 1994. Antiproliferative effect of baicalein, a flavonoid from a Chinese herb, on vascular smooth muscle cell. Eur J Pharmacol 251: 91-3.
    Ichihashi, M., Ueda, M., Budiyanto, A., Bito, T., Oka, M., Fukunaga, M., Tsuru, K. & Horikawa, T. 2003. UV-induced skin damage. Toxicology
    51
    189: 21-39.
    Ito, C., Itoigawa, M., Mishina, Y., Filho, V. C., Enjo, F., Tokuda, H., Nishino, H. & Furukawa, H. 2003. Chemical constituents of Calophyllum brasiliense. 2. Structure of three new coumarins and cancer chemopreventive activity of 4-substituted coumarins. J Nat Prod 66: 368-71.
    Jeong, T. S., Kim, K. S., Kim, J. R., Cho, K. H., Lee, S. & Lee, W. S. 2004. Novel 3,5-diaryl pyrazolines and pyrazole as low-density lipoprotein (LDL) oxidation inhibitor. Bioorg Med Chem Lett 14: 2719-23.
    Jezek, P. & Hlavata, L. 2005. Mitochondria in homeostasis of reactive oxygen species in cell, tissues, and organism. Int J Biochem Cell Biol 37: 2478-503.
    Justino, G. C., Santos, M. R., Canario, S., Borges, C., Florencio, M. H. & Mira, L. 2004. Plasma quercetin metabolites: structure-antioxidant activity relationships. Arch Biochem Biophys 432: 109-21.
    Kade, I. J., Paixao, M. W., Rodrigues, O. E., Barbosa, N. B., Braga, A. L., Avila, D. S., Nogueira, C. W. & Rocha, J. B. 2008. Comparative studies on dicholesteroyl diselenide and diphenyl diselenide as antioxidant agents and their effect on the activities of Na+/K+ ATPase and delta-aminolevulinic acid dehydratase in the rat brain. Neurochem Res 33: 167-78.
    Kakiuchi, Y., Sasaki, N., Satoh-Masuoka, M., Murofushi, H. & Murakami-Murofushi, K. 2004. A novel pyrazolone, 4,4-dichloro-1-(2,4-dichlorophenyl)-3-methyl-5-pyrazolone, as a potent catalytic inhibitor of human telomerase. Biochem Biophys Res Commun 320: 1351-1358.
    52
    Kanayasu-Toyoda, T., Morita, I. & Murota, S. 1998. Arachidonic acid pretreatment enhances smooth muscle cell migration via increased Ca2+ influx. Prostaglandins Leukot Essent Fatty Acids 58: 25-31.
    Karihtala, P. & Soini, Y. 2007. Reactive oxygen species and antioxidant mechanisms in human tissues and their relation to malignancies. APMIS 115: 81-103.
    Khan, I. A., Kulkarni, M. V., Gopal, M., Shahabuddin, M. S. & Sun, C. M. 2005. Synthesis and biological evaluation of novel angularly fused polycyclic coumarins. Bioorg Med Chem Lett 15: 3584-7.
    Khan, K. M., Saify, Z. S., Khan, M. Z., Zia, U., Choudhary, I. M., Atta Ur, R., Perveen, S., Chohan, Z. H. & Supuran, C. T. 2004. Synthesis of coumarin derivatives with cytotoxic, antibacterial and antifungal activity. J Enzyme Inhib Med Chem 19: 373-9.
    Kidane, A. G., Salacinski, H., Tiwari, A., Bruckdorfer, K. R. & Seifalian, A. M. 2004. Anticoagulant and antiplatelet agents: their clinical and device application(s) together with usages to engineer surfaces. Biomacromolecules 5: 798-813.
    Kimura, Y., Matsushita, N. & Okuda, H. 1997. Effects of baicalein isolated from Scutellaria baicalensis on interleukin 1 beta- and tumor necrosis factor alpha-induced adhesion molecule expression in cultured human umbilical vein endothelial cells. J Ethnopharmacol 57: 63-7.
    Kontogiorgis, C. & Hadjipavlou-Litina, D. 2003. Biological evaluation of several coumarin derivatives designed as possible anti-inflammatory/antioxidant agents. J Enzyme Inhib Med Chem 18: 63-9.
    53
    Kontogiorgis, C. A. & Hadjipavlou-Litina, D. J. 2004. Synthesis and biological evaluation of novel coumarin derivatives with a 7-azomethine linkage. Bioorg Med Chem Lett 14: 611-4.
    Kontogiorgis, C. A. & Hadjipavlou-Litina, D. J. 2005. Synthesis and antiinflammatory activity of coumarin derivatives. J Med Chem 48: 6400-8.
    Kostova, I. 2005. Synthetic and natural coumarins as cytotoxic agents. Curr Med Chem Anticancer Agents 5: 29-46.
    Lee, B. H., Clothier, M. F., Dutton, F. E., Conder, G. A. & Johnson, S. S. 1998. Anthelmintic beta-hydroxyketoamides (BKAs). Bioorg Med Chem Lett 8: 3317-20.
    Lee, K. H. 2004. Current developments in the discovery and design of new drug candidates from plant natural product leads. J Nat Prod 67: 273-83.
    Lin, H. C., Tsai, S. H., Chen, C. S., Chang, Y. C., Lee, C. M., Lai, Z. Y. & Lin, C. M. 2008. Structure-activity relationship of coumarin derivatives on xanthine oxidase-inhibiting and free radical-scavenging activities. Biochem Pharmacol 75: 1416-25.
    Lin, R., Chiu, G., Yu, Y., Connolly, P. J., Li, S., Lu, Y., Adams, M., Fuentes-Pesquera, A. R., Emanuel, S. L. & Greenberger, L. M. 2007a. Design, synthesis, and evaluation of 3,4-disubstituted pyrazole analogues as anti-tumor CDK inhibitors. Bioorg Med Chem Lett 17: 4557-61.
    Lin, Y. T., Yang, J. S., Lin, H. J., Tan, T. W., Tang, N. Y., Chaing, J. H., Chang, Y. H., Lu, H. F. & Chung, J. G. 2007b. Baicalein induces apoptosis in SCC-4 human tongue cancer cells via a Ca2+-dependent
    54
    mitochondrial pathway. In Vivo 21: 1053-8.
    Liu, H., Colavitti, R., Rovira, II & Finkel, T. 2005. Redox-dependent transcriptional regulation. Circ Res 97: 967-74.
    Liu, J. J., Huang, T. S., Cheng, W. F. & Lu, F. J. 2003. Baicalein and baicalin are potent inhibitors of angiogenesis: Inhibition of endothelial cell proliferation, migration and differentiation. Int J Cancer 106: 559-65.
    Liu, Z. Q., Yu, W. & Liu, Z. L. 1999. Antioxidative and prooxidative effects of coumarin derivatives on free radical initiated and photosensitized peroxidation of human low-density lipoprotein. Chem Phys Lipids 103: 125-35.
    Lloyd, R. V., Hanna, P. M. & Mason, R. P. 1997. The origin of the hydroxyl radical oxygen in the Fenton reaction. Free Radic Biol Med 22: 885-8.
    Maltese, A., Maugeri, F., Ward, K. W. & Bucolo, C. 2007. Development and validation of an RP-HPLC-UV method for the determination of BOL-303225-A, a new coumarin-based anti-inflammatory drug, in rat plasma. Biomed Chromatogr 21: 351-5.
    Martins, H. F., Leal, J. P., Fernandez, M. T., Lopes, V. H. & Cordeiro, M. N. 2004. Toward the prediction of the activity of antioxidants: experimental and theoretical study of the gas-phase acidities of flavonoids. J Am Soc Mass Spectrom 15: 848-61.
    Mates, J. M. & Sanchez-Jimenez, F. M. 2000. Role of reactive oxygen species in apoptosis: implications for cancer therapy. Int J Biochem Cell Biol 32: 157-70.
    Natarajan, R., Stern, N., Hsueh, W., Do, Y. & Nadler, J. 1988. Role of the lipoxygenase pathway in angiotensin II-mediated aldosterone biosynthesis in human adrenal glomerulosa cells. J Clin Endocrinol
    55
    Metab 67: 584-91.
    Nie, D., Krishnamoorthy, S., Jin, R., Tang, K., Chen, Y., Qiao, Y., Zacharek, A., Guo, Y., Milanini, J., Pages, G. & Honn, K. V. 2006. Mechanisms regulating tumor angiogenesis by 12-lipoxygenase in prostate cancer cells. J Biol Chem 281: 18601-9.
    Nishio, E. & Watanabe, Y. 1997. Role of the lipoxygenase pathway in phenylephrine-induced vascular smooth muscle cell proliferation and migration. Eur J Pharmacol 336: 267-73.
    Okuda, S., Saito, H. & Katsuki, H. 1994. Arachidonic acid: toxic and trophic effects on cultured hippocampal neurons. Neuroscience 63: 691-9.
    Postovit, L. M., Seftor, E. A., Seftor, R. E. & Hendrix, M. J. 2006. Influence of the microenvironment on melanoma cell fate determination and phenotype. Cancer Res 66: 7833-6.
    Raj, H. G., Parmar, V. S., Jain, S. C., Goel, S., Poonam, Himanshu, Malhotra, S., Singh, A., Olsen, C. E. & Wengel, J. 1998. Mechanism of biochemical action of substituted 4-methylbenzopyran-2-ones. Part I: Dioxygenated 4-methyl coumarins as superb antioxidant and radical scavenging agents. Bioorg Med Chem 6: 833-9.
    Rashba-Step, J., Turro, N. J. & Cederbaum, A. I. 1993. Increased NADPH- and NADH-dependent production of superoxide and hydroxyl radical by microsomes after chronic ethanol treatment. Arch Biochem Biophys 300: 401-8.
    Rice-Evans, C. A., Miller, N. J. & Paganga, G. 1996. Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med 20: 933-56.
    Saibara, T., Toda, K., Wakatsuki, A., Ogawa, Y., Ono, M. & Onishi, S. 2003.
    56
    Protective effect of 3-methyl-1-phenyl-2-pyrazolin-5-one, a free radical scavenger, on acute toxicity of paraquat in mice. Toxicol Lett 143: 51-4.
    Schuppan, D. & Popov, Y. 2002. Hepatic fibrosis: from bench to bedside. J Gastroenterol Hepatol 17 Suppl 3: S300-5.
    Sekiya, K. & Okuda, H. 1982. Selective inhibition of platelet lipoxygenase by baicalein. Biochem Biophys Res Commun 105: 1090-5.
    Sharma, S. D., Rajor, H. K., Chopra, S. & Sharma, R. K. 2005. Studies on structure activity relationship of some dihydroxy-4-methylcoumarin antioxidants based on their interaction with Fe(III) and ADP. Biometals 18: 143-54.
    Stohs, S. J. & Bagchi, D. 1995. Oxidative mechanisms in the toxicity of metal ions. Free Radic Biol Med 18: 321-36.
    Tao, J., Hu, S., Pacholec, M. & Walsh, C. T. 2003. Synthesis of proposed oxidation-cyclization-methylation intermediates of the coumarin antibiotic biosynthetic pathway. Org Lett 5: 3233-6.
    Verhaegen, M., Bauer, J. A., Martin de la Vega, C., Wang, G., Wolter, K. G., Brenner, J. C., Nikolovska-Coleska, Z., Bengtson, A., Nair, R., Elder, J. T., Van Brocklin, M., Carey, T. E., Bradford, C. R., Wang, S. & Soengas, M. S. 2006. A novel BH3 mimetic reveals a mitogen-activated protein kinase-dependent mechanism of melanoma cell death controlled by p53 and reactive oxygen species. Cancer Res 66: 11348-59.
    Wang, J., Yu, Y., Hashimoto, F., Sakata, Y., Fujii, M. & Hou, D. X. 2004. Baicalein induces apoptosis through ROS-mediated mitochondrial dysfunction pathway in HL-60 cells. Int J Mol Med 14: 627-32.
    57
    Winer, I., Normolle, D. P., Shureiqi, I., Sondak, V. K., Johnson, T., Su, L. & Brenner, D. E. 2002. Expression of 12-lipoxygenase as a biomarker for melanoma carcinogenesis. Melanoma Res 12: 429-34.
    Wu, C., Chen, F., Wang, X., Wu, Y., Dong, M., He, G., Galyean, R. D., He, L. & Huang, G. 2007. Identification of antioxidant phenolic compounds in feverfew (Tanacetum parthenium) by HPLC-ESI-MS/MS and NMR. Phytochem Anal 18: 401-10.
    Wu, W. S. 2006. The signaling mechanism of ROS in tumor progression. Cancer Metastasis Rev 25: 695-705.
    Xanthoudakis, S., Miao, G., Wang, F., Pan, Y. C. & Curran, T. 1992. Redox activation of Fos-Jun DNA binding activity is mediated by a DNA repair enzyme. EMBO J 11: 3323-35.
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