1.行政院衛生署 中華民國一〇一年死因統計; 行政院衛生署: 行政院衛生署, 2012.
2.Fan, C. L.; Lay, J. G., Spatial relations between environmental pollution and malignant tumors - A case study of liver cancer and lung cancer on cancer map. Journal of Cartography 2006, 16, 205-220.
3.Evan, G. I.; Vousden, K. H., Proliferation, cell cycle and apoptosis in cancer. Nature 2001, 411, 342-348.
4.Roche, V. F., Cancer and Chemotherapy. In Foye''s Principles of Medicinal Chemistry, Lemke, T. L.; Williams, D. A.; Roche, V. F.; Zito, S. W., Eds. Lippincott Williams & Wilkins: 2013; pp 1199-1267.
5.Patrick, G. L., Anticancer agnets. In An Introduction of Medicinal Chemistry, Patrick, G. L., Ed. Oxford University: New York, 2009; pp 519-578.
6.www.abcam.com
7.McGrogan, B. T.; Gilmartin, B.; Carney, D. N.; McCann, A., Taxanes, microtubules and chemoresistant breast cancer. Biochim. Biophys. Acta 2008, 1785 (2), 96-132.
8.Jordan, M. A.; Wilson, L., Microtubules as a target for anticancer drugs. Nat. Rev. Cancer 2004, 4, 253-265.
9.Cordell, G. A., The Alkaloids: Chemistry and Biology. 2007; pp. 139-214.
10.Holton, R. A.; Somoza, C.; Kim, H. B.; Liang, F.; Biediger, R. J.; Boatman, P. D.; Shindo, M.; Smith, C. C.; Kim, S., First total synthesis of taxol. 1. Functionalization of the B ring. J. Am. Chem. Soc. 1994, 116 (4), 1597-1598.
11.Holton, R. A.; Kim, H. B.; Somoza, C.; Liang, F.; Biediger, R. J.; Boatman, P. D.; Shindo, M.; Smith, C. C.; Kim, S., First total synthesis of taxol. 2. Completion of the C and D rings. J. Am. Chem. Soc. 1994, 116 (4), 1599-1600.
12.Holton, R. A.; Juo, R. R.; Kim, H. B.; Williams, A. D.; Harusawa, S.; Lowenthal, R. E.; Yogai, S., A synthesis of taxusin. J. Am. Chem. Soc. 1988, 110 (19), 6558-6560.
13.Nicolaou, K. C.; Dai, W.-M.; Guy, R. K., Chemistry and biology of taxol. Angew. Chem. Int. Ed. Engl. 1994, 33 (1), 15-44.
14.李力更; 吳明; 史清文, 天然抗癌藥物紫杉醇的全合成. Nat. Prod. Res. Dev. 2008, 1113, 1104-1107.
15.Nicolaou, K. C.; Yang, Z.; Liu, J. J.; Ueno, H.; Nantermet, P. G.; Guy, R. K.; Claiborne, C. F.; Renaud, J.; Couladouros, E. A.; Paulvannan, K.; et al., Total synthesis of taxol. Nature 1994, 367 (6464), 630-634.
16.Nicolaou, K. C.; Nantermet, P. G.; Ueno, H.; Guy, R. K.; Couladouros, E. A.; Sorensen, E. J., Total synthesis of taxol. 1. Retrosynthesis, degradation, and reconstitution. J. Am. Chem. Soc. 1995, 117 (2), 624-633.
17.Danishefsky, S. J.; Masters, J. J.; Young, W. B.; Link, J. T.; Snyder, L. B.; Magee, T. V.; Jung, D. K.; Isaacs, R. C. A.; Bornmann, W. G.; Alaimo, C. A.; Coburn, C. A.; Di Grandi, M. J., Total synthesis of Baccatin III and taxol. J. Am. Chem. Soc. 1996, 118 (12), 2843-2859.
18.Wender, P. A.; Badham, N. F.; Conway, S. P.; Floreancig, P. E.; Glass, T. E.; Houze, J. B.; Krauss, N. E.; Lee, D.; Marquess, D. G.; McGrane, P. L.; Meng, W.; Natchus, M. G.; Shuker, A. J.; Sutton, J. C.; Taylor, R. E., The Pinene Path to Taxanes. 6. A concise stereocontrolled synthesis of taxol. J. Am. Chem. Soc. 1997, 119 (11), 2757-2758.
19.Morihira, K.; Hara, R.; Kawahara, S.; Nishimori, T.; Nakamura, N.; Kusama, H.; Kuwajima, I., Enantioselective Total synthesis of taxol. J. Am. Chem. Soc. 1998, 120 (49), 12980-12981.
20.Kusama, H.; Hara, R.; Kawahara, S.; Nishimori, T.; Kashima, H.; Nakamura, N.; Morihira, K.; Kuwajima, I., Enantioselective total synthesis of (−)-taxol. J. Am. Chem. Soc. 2000, 122 (16), 3811-3820.
21.Shiina, I.; Iwadare, H.; Sakoh, H.; Hasegawa, M.; Tani, Y.-i.; Mukaiyama, T., A new method for the synthesis of Baccatin III. Chem. Lett. 1998, 27 (1), 1-2.
22.Mukaiyama, T.; Shiina, I.; Iwadare, H.; Saitoh, M.; Nishimura, T.; Ohkawa, N.; Sakoh, H.; Nishimura, K.; Tani, Y.-i.; Hasegawa, M.; Yamada, K.; Saitoh, K., Asymmetric total synthesis of taxol Chem. Eur. J.1999, 5 (1), 121-161.
23.Doi, T.; Fuse, S.; Miyamoto, S.; Nakai, K.; Sasuga, D.; Takahashi, T., A formal total synthesis of taxol aided by an automated synthesizer. Chem. Asian J. 2006, 1 (3), 370-383.
24.Thomas, G., Drugs from natural sources. In Medicinal Chemistry-An introduction, Thomas, G., Ed. Wiley: 2007; pp 202-206.
25.Mann, J., Natural products in cancer chemotherapy: past, present and future. Nat. Rev. Cancer 2002, 2 (2), 143-148.
26.Long, B. H.; Carboni, J. M.; Wasserman, A. J.; Cornell, L. A.; Casazza, A. M.; Jensen, P. R.; Lindel, T.; Fenical, W.; Fairchild, C. R., Eleutherobin, a novel cytotoxic agent that induces tubulin polymerization, is similar to Paclitaxel (Taxol®). Cancer Res. 1998, 58 (6), 1111-1115.
27.Cheng, K. L.; Bradley, T.; Budman, D. R., Novel microtubule-targeting agents – the epothilones. Biologics: Targets & Therapy 2008, 2 (4), 789-811.
28.Kruczynski, A.; Barret, J. M.; Etievant, C.; Colpaert, F.; Fahy, J.; Hill, B. T., Antimitotic and tubulin-interacting properties of vinflunine, a novel fluorinated vinca alkaloid. Biochem. Pharmacol. 1998, 55 (5), 635-648.
29.Begue, J.-P.; Bonnet-Delpon, D., Fluorinated analogues of natural products. In Bioorganic and Medicinal Chemistry of Fluorine Begue, J.-P.; Bonnet-Delpon, D., Eds. Wiley: 2008; pp 99-139.
30.Jackson, J. R.; Patrick, D. R.; Dar, M. M.; Huang, P. S., Targeted anti-mitotic therapies: can we improve on tubulin agents? Nat. Rev. Cancer 2007, 7 (2), 107-117.
31.http://clinicaltrials.gov/ (美國政府臨床試驗網站)
32.http://www.fda.gov/(美國FDA網站)
33.吳永昌; 蘇燦隆, 抗癌天然藥物的研發. CHEMISTRY 2004, 62 (2), 173-18634.楊兆琪, 抗癌药Combretastatin A-4 结构修饰的研究进展. 化学通报 2006, 69.
35.http://en.wikipedia.org/wiki/Discovery_and_development_of_tubulin_inhibitors
36.Ball, M.; Gaunt, M. J.; Hook, D. F.; Jessiman, A. S.; Kawahara, S.; Orsini, P.; Scolaro, A.; Talbot, A. C.; Tanner, H. R.; Yamanoi, S.; Ley, S. V., Total synthesis of spongistatin 1: A synthetic strategy exploiting its latent pseudo-symmetry. Angew. Chem. Int. Ed. 2005, 44 (34), 5433-5438.
37.Corey, E. J.; Weigel, L. O.; Chamberlin, A. R.; Cho, H.; Hua, D. H., Total synthesis of maytansine. J. Am. Chem. Soc. 1980, 102 (21), 6613-6615.
38.Danner, P.; Bauer, M.; Phukan, P.; Maier, Martin E., Total synthesis of cryptophycin 3. Eur. J. Org. Chem. 2005, 2005 (2), 317-325.
39.Smith, A. B.; Fukui, M.; Vaccaro, H. A.; Empfield, J. R., Phyllanthoside-phyllanthostatin synthetic studies. 7. Total synthesis of (+)-phyllanthocin and (+)-phyllanthocindiol. J. Am. Chem. Soc. 1991, 113 (6), 2071-2092.
40.Smith, A. B.; Zhu, W.; Shirakami, S.; Sfouggatakis, C.; Doughty, V. A.; Bennett, C. S.; Sakamoto, Y., Total synthesis of (+)-spongistatin 1. An effective second-generation construction of an advanced EF wittig salt, fragment union, and final elaboration. Org. Lett. 2003, 5 (5), 761-764.
41.Wu, T. S., Alkaloids and coumarins of Skimmia reevesiana. Phytochemistry 1987, 26, 873-875.
42.Awaad, A.; Maitland, D.; Moneir, S., New alkaloids from Casimiroa edulis fruits and their pharmacological activity. Chem. Nat. Compd. 2007, 43 (5), 576-580.
43.Rizvi, S. H.; Kapil, R. S.; Shoeb, A., Alkaloids and coumarins of Casimiroa edulis. J. Nat. Prod. 1985, 48 (1), 146.
44.Lozoya-Legorreta, X.; Rodriguez-Reynaga, D.; Ortega-Galvan, J.; Enriquez-Habib, R., Isolation of a hypotensive substance from seeds of Casimiroa edulis. Arch. Invest. Med. 1978, 9 (4), 565-73.
45.Kuo, S. C.; Lee, H. Z.; Juang, J. P.; Lin, Y. T.; Wu, T. S.; Chang, J. J.; Lednicer, D.; Paull, K. D.; Lin, C. M.; Hamel, E.; Lee, K. H., Synthesis and cytotoxicity of 1,6,7,8-substituted 2-(4''-substituted phenyl)-4-quinolones and related compounds: identification as antimitotic agents interacting with tubulin. J. Med. Chem. 1993, 36 (9), 1146 - 1156.
46.Chou, L. C.; Tsai, M. T.; Hsu, M. H.; Lin, H. Y.; Huang, L. J.; Kuo, S. C.; Wang, S. H.; Way, T. D.; Huang, C. H.; Qian, K.; Dong, Y.; Lee, K.-H., Design, synthesis, and preclinical evaluation of new 5,6- (or 6,7-) disubstituted-2-(fluorophenyl)quinolin-4-one derivatives as potent antitumor agents. J. Med. Chem. 2010, 53 (22), 8047 - 8058.
47.Li, L.; Wang, H. K.; Kuo, S. C.; Wu, T. S.; Mauger, A.; Lin, C. M.; Hamel, E.; Lee, K.-H., Antitumor agents 155. synthesis and biological evaluation of 3'',6,7-substituted 2-phenyl-4-quinolones as antimicrotubule agents. J. Med. Chem. 1994, 37 (20), 3400-3407.
48.Chou, L. C.; Chen, C. T.; Lee, J. C.; Huang, S. M.; Huang, L. J.; Kuo, S. C.; Qian, K.; Morris-Natschke, S. L.; Lee, K. H.; Way, T. D.; Huang, C. H.; Teng, C. M.; Yamori, T.; Wu, T. S.; Sun, C. M.; Chien, D.-S., Synthesis and preclinical evaluations of 2-(2-fluorophenyl)-6,7- methylenedioxyquinolln-4-one monosodium phosphate (CHM-I-P-Na) as a potent antitumor agent. J. Med. Chem. 2010, 53 (4), 1616 - 1626.
49.Chen, C. T.; Hsu, M. H.; Cheng, Y. Y.; Liu, C. Y.; Chou, L. C.; Huang, L. J.; Wu, T. S.; Yang, X.; Lee, K. H.; Kuo, S. C., Synthesis and in vitro anticancer activity of 6,7-methylenedioxy (or 5-hydroxy-6-methoxy)-2-(substituted selenophenyl)quinolin-4-one analogs. Eur. J. Med. Chem. 2011, 46 (12), 6046-6056.
50.Xia, Y.; Yang, Z. Y.; Xia, P.; Hackl, T.; Hamel, E.; Mauger, A.; Wu, J. H.; Lee, K. H., Antitumor agents. 211. fluorinated 2-phenyl-4-quinolone derivatives as antimitotic antitumor agents. J. Med. Chem. 2001, 44 (23), 3932-3936.
51.Xia, Y.; Yang, Z. Y.; Xia, P.; Bastow, K. F.; Nakanishi, Y.; Nampoothiri, P.; Hamel, E.; Brossi, A.; Lee, K. H., Antitumor agents. Part 226: synthesis and cytotoxicity of 2-phenyl-4-quinolone acetic acids and their esters. Bioorg. Med. Chem. Lett. 2003, 13 (17), 2891-2893.
52.Lai, Y. Y.; Huang, L. J.; Lee, K. H.; Xiao, Z.; Bastow, K. F.; Yamori, T.; Kuo, S. C., Synthesis and biological relationships of 3'',6-substituted 2-phenyl-4-quinolone-3-carboxylic acid derivatives as antimitotic agents. Bioorg. Med. Chem. 2005, 13 (1), 265-276.
53.Li, L.; Wang, H. K.; Kuo, S. C.; Wu, T. S.; Lednicer, D.; Lin, C. M.; Hamel, E.; Lee, K.-H., Antitumor agents. 150. 2'',3'',4'',5'',5,6,7-substituted 2-phenyl-4-quinolones and related compounds: their synthesis, cytotoxicity, and inhibition of tubulin polymerization. J. Med. Chem. 1994, 37 (8), 1126-1135.
54.Chang, Y. H.; Hsu, M. H.; Wang, S. H.; Huang, L. J.; Qian, K.; Morris-Natschke, S. L.; Hamel, E.; Kuo, S. C.; Lee, K. H., Design and synthesis of 2-(3-benzo[b]thienyl)-6,7-methylenedioxyquinolin-4-one analogues as potent antitumor agents that inhibit tubulin assembly. J. Med. Chem. 2009, 52 (15), 4883-4891.
55.Chen, K.; Kuo, S. C.; Hsieh, M. C.; Mauger, A.; Lin, C. M.; Hamel, E.; Lee, K. H., Antitumor agents. 174. 2‘,3‘,4‘,5,6,7-substituted 2-phenyl-1,8-naphthyridin-4-ones: their synthesis, cytotoxicity, and inhibition of tubulin polymerization1. J. Med. Chem. 1997, 40 (14), 2266-2275.
56.Chen, K.; Kuo, S. C.; Hsieh, M. C.; Mauger, A.; Lin, C. M.; Hamel, E.; Lee, K.-H., Antitumor agents. 178. synthesis and biological evaluation of substituted 2-aryl-1,8-naphthyridin-4(1H)-ones as antitumor agents that inhibit tubulin polymerization. J. Med. Chem. 1997, 40 (19), 3049-3056.
57.Zhang, S. X.; Bastow, K. F.; Tchibana, Y.; Kuo, S. C.; Hamel, E.; Mauger, A.; Narayanan, V. L.; Lee, K.-H., Antitumor agents. 196. substituted 2-thienyl-1,8-naphthyridin-4-ones: their synthesis, cytotoxicity, and inhibition of tubulin polymerization. J. Med. Chem. 1999, 42 (20), 4081-4087.
58.Hour, M. J.; Huang, L. J.; Kuo, S. C.; Xia, Y.; Bastow, K.; Nakanishi, Y.; Hamel, E.; Lee, K. H., 6-Alkylamino- and 2,3-dihydro-3‘-methoxy-2-phenyl-4-quinazolinones and related compounds: their synthesis, cytotoxicity, and inhibition of tubulin polymerization. J. Med. Chem. 2000, 43 (23), 4479-4487.
59.Xia, Y.; Yang, Z. Y.; Hour, M. J.; Kuo, S. C.; Xia, P.; Bastow, K. F.; Nakanishi, Y.; Nampoothiri, P.; Hackl, T.; Hamel, E.; Lee, K. H., Antitumor agents. part 204: synthesis and biological evaluation of substituted 2-aryl quinazolinones. Bioorg. Med. Chem. Lett. 2001, 11 (9), 1193-1196.
60.Xia, Y.; Yang, Z. Y.; Xia, P.; Bastow, K. F.; Tachibana, Y.; Kuo, S.-C.; Hamel, E.; Hackl, T.; Lee, K. H., Antitumor Agents. 181.+ Synthesis and biological evaluation of 6,7,2‘,3‘,4‘-substituted-1,2,3,4-tetrahydro-2-phenyl-4-quinolones as a new class of antimitotic antitumor agents. J. Med. Chem. 1998, 41 (7), 1155-1162.
61.Lee, J. C.; Chou, L. C.; Huang, C. H.; Chung, J. G.; Huang, L. J.; Lee, K. H.; Hung, M. C.; Way, T. D.; Kuo, S. C., CHM-1 induces apoptosis via p38-mediated upregulation of DR5 expression in human ovarian cancer SKOV3 cells. Eur. J. Pharmacol. 2011, 670 (1), 96-104.
62.Chen, H. Y.; Lu, H. F.; Yang, J. S.; Kuo, S. C.; Lo, C.; Yang, M. D.; Chiu, T. H.; Chueh, F. S.; Ho, H. C.; Ko, Y. C.; Chung, J. G., The novel quinolone CHM-1 induces DNA damage and inhibits DNA repair gene expressions in a human osterogenic sarcoma cell line. Anticancer Res. 2010, 30 (10), 4187-4192.
63.Chou, L. C.; Yang, J. S.; Huang, L. J.; Wu, H. C.; Lu, C. C.; Chiang, J. H.; Chen, K. T.; Kuo, S. C.; Chung, J. G., The synthesized 2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-one (CHM-1) promoted G2/M arrest through inhibition of CDK1 and induced apoptosis through the mitochondrial-dependent pathway in CT-26 murine colorectal adenocarcinoma cells. J. Gastroenterol. 2009, 44 (10), 1055-1063.
64.Wang, S. W.; Pan, S. L.; Huang, Y. C.; Guh, J. H.; Chiang, P. C.; Huang, D. Y.; Kuo, S. C.; Lee, K. H.; Teng, C. M., CHM-1, a novel synthetic quinolone with potent and selective antimitotic antitumor activity against human hepatocellular carcinoma in vitro and in vivo. Mol. Cancer Ther. 2008, 7 (2), 350-360.
65.Wang, S. W.; Pan, S. L.; Peng, C. Y.; Huang, D. Y.; Tsai, A. C.; Chang, Y.-L.; Guh, J.-H.; Kuo, S.-C.; Lee, K.-H.; Teng, C.-M., CHM-1 inhibits hepatocyte growth factor-induced invasion of SK-Hep-1 human hepatocellular carcinoma cells by suppressing matrix metalloproteinase-9 expression. Cancer Letters 2007, 257 (1), 87-96.
66.Heimbach, T.; Oh, D.M.; Li, L.Y.; Forsberg, M.; Savolainen, J.; Leppanen, J.; Matsunaga, Y.; Flynn, G.; Fleisher, D. Absorption rate limit considerations for oral phosphate prodrugs. Pharm. Res. 2003, 20, 848-856.
67.Fleisher, D.; Bong, R.; Stewartb, B.H. Improved oral drug delivery: solubility limitations overcome by use of prodrugs. Adv. Drug Deliv. Rev. 1996, 19, 115-130.
68.Kearney, A.S. Prodrugs and targeted drug delivery. Adv. Drug Deliv. Rev. 1996, 19, 225-239.
69.Stella, V.J. A case for prodrugs: Fosphenytoin. Adv. Drug Deliv. Rev. 1996, 19, 311-330.
70.Rautio, J.; Kumpulainen, H.; Heimbach, T.; Oliyai, R.; Oh, D.; Jarvinen, T.; Savolainen, J. Prodrugs: design and clinical applications. Nat. Rev. Drug Discov. 2008, 7, 255-270.
71.Heimbach, T., Fleisher, D., Kaddoumi, A., Overcoming poor aqueous solubility of drugs for oral delivery. In Prodrugs: Challenges and Rewards Part 1, Stella, V.J.; Borchardt, R.T.; Hageman, M.J.; Oliyai, R.; Maag, H.; Tilley, J.W., Eds. Springer: New York, 2007; pp 157-215.
72.Sherwood, R.F. Advanced drug delivery reviews: enzyme prodrug therapy. Adv. Drug Deliv. Rev. 1996, 22, 269-288.
73.Stella, V.J., Borchardt, R.T., Hageman, M.J., Oliyai, R., Maag, H., and Tilley, J.W., A Case for prodrugs. In Prodrugs: Challenges and Rewards Part 1, Stella, V.J., Borchardt, R.T., Hageman, M.J., Oliyai, R., Maag, H., and Tilley, J.W., Ed. Springer: New York, 2007; Vol. Part 1, pp 3-33.
74.Spitaleri, G.; Matei, D. V.; Curigliano, G.; Detti, S.; Verweij, F.; Zambito, S.; Scardino, E.; Rocco, B.; Nole, F.; Ariu, L.; De Pas, T.; de Braud, F.; De Cobelli, O., Phase II trial of estramustine phosphate and oral etoposide in patients with hormone-refractory prostate cancer. ESMO 2009, 20, 498-502.
75.Levitt, N. C.; Propper, D. J.; Madhusudan, S.; Braybrooke, J. P.; Echeta, C.; Te Poele, R.; Davies, S. L.; Flanagan, E.; Hickson, I. D.; Joel, S.; Ganesan, T. S., Pharmacokinetically guided phase I trial of topotecan and etoposide phosphate in recurrent ovarian cancer. Brit. J. Cancer 2005, 93, 60-69.
76.Witterland, A. H.; Koks, C. H.; Beijnen, J. H., Etoposide phosphate, the water soluble prodrug of etoposide. PWS 1996, 18, 163-170.
77.Simoni, D.; Romagnoli, R.; Baruchello, R.; Rondanin, R.; Rizzi, M.; Pavani, M.G.; Alloatti, D.; Giannini, G.; Marcellini, M.; Riccioni, T.; Castorina, M.; Guglielmi, M. B.; Bucci, F.; Carminati, P.; Pisano, C. Novel combretastatin analogues endowed with antitumor activity. J. Med. Chem. 2006, 49, 3143-3152.
78.Bedford, S. B.; Quarterman, C. P.; Rathbone, D. L.; Slack, J. A. Synthesis of water-soluble prodrugs of the cytotoxic agent combretastin A4. Bioorg. Med. Chem. Lett. 1996, 6, 157-160.
79.Heimbach, T.; Oh, D. M.; Li, L. Y.; Rodriguez-Hornedo, N.; Garcia, G.; Fleisher, D., Enzyme-mediated precipitation of parent drugs from their phosphate prodrugs. Int. J. Pharm. 2003, 261, 81-92.
80.Yuan, H.; Li, N.; Lai, Y., Evaluation of in vitro models for screening alkaline phosphatase-mediated bioconversion of phosphate ester prodrugs. Drug Metab. Dispos. 2009, 37, 1443-1447.
81.Chen, K.; Wang, K.; Kirichian, A. M.; Al Aowad, A. F.; Iyer, L. K.; Adelstein, S. J.; Kassis, A. I., In silico design, synthesis, and biological evaluation of radioiodinated quinazolinone derivatives for alkaline phosphatase-mediated cancer diagnosis and therapy. Mol. Cancer Ther. 2006, 5, 3001-3013.
82.de Jong, R. S.; Slijfer, E. A.; Uges, D. R.; Mulder, N. H.; de Vries, E. G., Conversion of the prodrug etoposide phosphate to etoposide in gastric juice and bile. Brit. J. Cancer 1997, 76 (11), 1480-1483.
83.Suzuki, H.; Iino, S.; Endo, Y.; Torii, M.; Miki, K., Tumor-specific alkaline phosphatase in hepatoma. Annals of the New York Academy of Sciences 1975, 259, 307-320.
84.Cha, M. C.; Lin, A.; Meckling, K. A., Low dose docosahexaenoic acid protects normal colonic epithelial cells from araC toxicity. BMC pharmacology 2005, 5, 7