Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/3948
標題: BODIPY衍生物之合成、光學性質探討與光動力治療之應用
Synthesis and Optical Investigation of BODIPY-derivative for Selective Photodynamic Therapy
作者: 賴彥池
Lai, Yen-Chih
關鍵字: 光動力治療
PDT
光穩定性
BODIPY
Photostability
出版社: 生醫工程研究所
引用: 1. (a)G. W. Kim , M. J. Cho , Y.J. Yu , Z. H. Kim , J.I Jin , D. Y. Kim , D. H . Choi . Chem. Mater. 2007, 19, 42-50. (b) L. Yang , J .K . Feng , A. M. Ren. J. Org.Chem. 2005, 70 (15), 5987 -5996. 2. Sheri Madhu, Rajesh Gonnade, and Mangalampalli Ravikanth. J. Org. Chem. 2013, 78, 5056−5060. 3. Li-Ya. Niu, Ying-Shi. Guan, Yu-Zhe. Chen, Li-Zhu. Wu, Chen-Ho. Tung, and Qing-Zheng. Yang. J. Am. Chem. Soc.,2012,134(46), 18928–18931. 4. Dongping Wang, Yasuhiro Shiraishi and Takayuki Hirai. Chem. Commun., 2011, 47, 2673–2675. 5. Ha. Na. Kim, Wen. Xiu. Ren, Jong. Seung. Kim and Juyoung Yoon. Chem. Soc. Rev., 2012, 41, 3210–3244. 6. Jihye Park and Youngmi Kim. Analyst, 2012, 137, 3246–3248. 7. (a) A. C. S. Samia, X. Chen, C Burda. J. Am. Chem. Soc.; 2003; 125(51);15736-15737 (b)F. Yukruk, A. L. Dogan, H Canpinar, D. Guc, E. U. Akkaya. Org. Lett.;2005; 7(14); 2885-2887 (c) P Zhang, W Steelant, M Kumar, M. Scholfield. J. Am. Chem. Soc.; 2007; 129(15); 4526-4527. 8. Dennis E.J.G.J. Dolmans, Dai Fukumura, Rakesh K. Jain, Nature Reviews Cancer,380-387, 2003. 9. 光連雙月刊.2006.05 63期 、光電科技工業協進會. 10. Treibs .A. Kreuzer, F. H. Justus Liebigs. Ann. Chem. 1968, 718,208. 11. M. Rajeswara Rao, K.V. Pavan Kumar, M. Ravikanth. Journal of Organometallic Chemistry 695, 2010 863–869. 12. Taoufik Rohand, Mukulesh Baruah, Wenwu Qin, Noe‥l Boens and Wim Dehaen. Chem. Commun., 2006, 266–268. 13. Tamanna K. Khan, M. Ravikanth. Tetrahedron. 67, 2011 5816~5824. 14. Taoufik Rohand, Wenwu Qin, Noel Boens, and Wim Dehaen. Eur. J. Org. Chem. 2006, 4658–4663. 15. Li-Ya Niu, Ying-Shi Guan, Yu-Zhe Chen, Li-Zhu Wu, Chen-Ho Tung, and Qing-Zheng Yang. J. Am. Chem. Soc. 2012, 134, 18928−18931 16. Si Zhang, Tong Wu, Jiangli Fan, Zhiyong Li, Na Jiang, Jingyun Wang Bairui Dou, Shiguo Sun, Fengling Songa and Xiaojun Peng. Org. Biomol. Chem., 2013, 11, 555–558. 17. (a)G. W. Kim, M. J. Cho, Y. J. Yu, Z. H. Kim, J. I. Jin, D. Y. Kim, D. H. Choi. Chem. Mater. 2007, 19, 42-50. (b) L. Yang, J. K. Feng, A. M. Ren. J. Org. Chem. 2005, 70 (15), 5987 -5996. 18. Theodore Lazarides, Georgios Charalambidis, Alexandra Vuillamy, Marius 83 Reglier, Emmanuel Klontzas, Georgios Froudakis, Susanne Kuhri, Dirk M. Guldi, and Athanassios G. Coutsolelos. Inorg. Chem. 2011, 50, 8926–8936. 19. (a) C.O. Okafor. Dyes and Pigments,1986, 7, 249. (b)J. J. Aaron,Maafi M.;Kersebet, C.; Parkanyi, C.; Antonious, M.S.; Motohashi. N. Photochem. Photobiol. A. 1996, 101 127-136. 20. Okamoto, T. Kuratsu, M. Kozaki, M. Hirotsu, K. Ichimura, A. Matsushita, T.Okada, K. Org. Lett. 2004, 6 (20), 3493-3496. 21. Hui He and Dennis K. P. Ng. Org. Biomol. Chem., 2011, 9, 2610–2613 . 22. Yongchao Yang, Qiuli Guo, Huachao Chen, Zhikuan Zhou, Zijian Guo and Zhen Shen. Chem. Commun., 2013,49, 3940-3942. 23. Mani Vedamalai and Shu-Pao Wu. Org. Biomol. Chem., 2012, 10, 5410–5416. 24. Huimin Guo, Yingying Jing, Xiaolin Yuan, Shaomin Ji, Jianzhang Zhao, Xiaohuan Li and Yanyan Kan. Org. Biomol. Chem., 2011, 9, 3844–3853. 25. Anyanee Kamkaew, Siang Hui Lim, Hong Boon Lee, Lik Voon Kiew,Lip Yong Chung and Kevin Burgess. Chem. Soc. Rev., 2013, 42, 77—88. 26. T. Yogo, Y. Urano, Y. Ishitsuka, F. Maniwa and T. Nagano, J. Am.Chem. Soc., 2005, 127, 12162–12163. 27. S. H. Lim, C. Thivierge, P. Nowak-Sliwinska, J. Han, H. Van denBergh, G. Wagnieres, K. Burgess and H. B. Lee, J. Med. Chem., 2010,53, 2865–2874. 28. M. Wainwright, D. A. Phoenix, L. Rice, S. M. Burrow and J. Waring, J Photochem. Photobiol., B, 1997, 40, 233–239. 29. (a) Schweitzer, C.; Schmidt, R. Chem. ReV. 2003, 103, 1685–1757.(b) Koziar, J. C.; Cowan, D. O. Acc. Chem. Res. 1978, 334–341. 30. Sauerwein, B.; Schuster, G. B. J. Phys. Chem. 1991, 95, 1903–1906. 31. M. J. Ortiz, A. R. Agarrabeitia, G. Duran-Sampedro, J. BanuelosPrieto, T. A. Lopez, W. A. Massad, H. A. Montejano, N. A. Garcia and I. Lopez Arbeloa, Tetrahedron, 2012, 68, 1153–1162. 32. W. Wu, H. Guo, W. Wu, S. Ji and J. Zhao, J. Org. Chem., 2011, 76,7056–7064. 33. J. Killoran, L. Allen, J. F. Gallagher, W. M. Gallagher andD. F. O’Shea, Chem. Commun., 2002, 1862–1863. 34. A. Gorman, J. Killoran, C. O’Shea, T. Kenna, W. M. Gallagher andD. F. O’Shea, J. Am. Chem. Soc., 2004, 126, 10619–10631. 35. Lijuan Jiao, Weidong Pang, Jinyuan Zhou, Yun Wei, Xiaolong Mu, Guifeng Bai, and Erhong Hao J. Org. Chem.,2011,76(24), 9988–9996. 36. Siang Hui Lim, Cliferson Thivierge, Patrycja Nowak-Sliwinska, Junyan Han, Hubert van den Bergh, Georges Wagnieres, Kevin Burgess and Hong Boon Lee J. Med. Chem.,2010,53(7), 2865–2874 37. Si Zhang,Tong Wu,Jiangli Fan,Zhiyong Li,Na Jiang,Jingyun Wang,Bairui Dou,Shiguo Sun,Fengling Song and Xiaojun Peng. Org. Biomol. Chem., 2013,11, 555-558. 38. Serdar Atilgan, Zeynep Ekmekci, A. Lale Dogan, Dicle Guc and Engin U. Akkaya. Chem. Commun., 2006, 4398–4400. 39. Yongchao Yang, Qiuli Guo, Huachao Chen, Zhikuan Zhou,Zijian Guo and Zhen Shen. Chem. Commun., 2013, 49, 3940-3942. 40. Hui He, Pui-Chi Lo, Sin-Lui Yeung, Wing-Ping Fong, and Dennis K. P. Ng. J. Med. Chem. 2011, 54, 3097–3102. 41. Nagappanpillai Adarsh, Rekha R. Avirah, and Danaboyina Ramaiah. Org. Lett.,2010,(24), 5720–5723. 42. Takatoshi Yogo, Yasuteru Urano, Yukiko Ishitsuka, Fumio Maniwa, and Tetsuo Nagano. J. Am. Chem. Soc.,2005,127(35), 12162–12163 43. Onur Buyukcakir,O. Altan Bozdemir,Safacan Kolemen,Sundus Erbas,and Engin U. Akkaya. Org. Lett 2009, 11, (20) 4644-4647 44. Sekai Tombe, Wadzanai Chidawanyika, Edith Antunes, Georgios Priniotakis, Philippe Westbroek, Tebello Nyokong. Journal of Photochemistry and Photobiology A: Chemistry 240 (2012) 50–58 45. Russell B. Vegh, Kyril M. Solntsev,Marina K. Kuimova,Soohee Cho, Yue Liang,Bernard L. W. Loo, Laren M. Tolberta and Andreas S. Bommarius. Chem. Commun., 2011, 47, 4887–4889 46. Skoog, D A.; Holler, E. J.; Nieman, T. A. Principles of Instrumental Analysis, 5th ed. Saunders College Publishing, 1998,355. 47. Friedrich Vollmer,Wolfgang Rettig, Eckhard Birckner. Journal of Fluorescence. 1994, 4,(1) 65-69.
摘要: 在此論文中,我們成功合成出一系列以BODIPY 為主體並具有光穩定和高光 學效率特性之光敏感物質,而這些光敏感物質具有偵測酸濃度、在光源照射下同 時產生單重態氧與超氧化物之能力。另外,藉由調控合成步驟搭配使用較便宜之 起始物,我們可以很輕易的合成出不同取代位置之BODIPY 衍生物。此外,在 生物實驗中,藉由觀察化合物在細胞中的攝取量、所待胞器位置和光毒性,我們 可以發現到化合物5b 和8a 在光動力治療中對於癌細胞的毒殺能力遠大於正常細 胞,且沒有觀察到明顯之暗毒性,因此我們認為化合物5b 和8a 在選擇性光動力 治療上是很有潛力的,而在文獻中,BODIPY 分子具有此特性是很罕見的。另外, 跟市售之光敏感物質做比較,可發現所合成出來之化合物與methylene blue 具有 相似之光毒性效果,而遠大於Foscan。 BODIPY 分子具有許多卓越的光學特性。在本研究中,透過觀察溶液的顏色變 化與螢光增強現象,具有可酸化官能基的化合物可被應用於在水溶液和有機溶劑 中偵測酸濃度之變化。此外,我們成功的將BODIPY 衍生物應用於癌症標靶上, 並證明化合物5b 和8a 在光動力治療中對腫瘤專一性方面是具有潛力的光敏感物 質。因此,在此研究中主要有以下特色,第一:我們提出便宜又方便的合成步驟, 可廣泛的應用於多元的BODIPY 衍生物合成。第二:藉由觀察ROS 的產生、細 胞對化合物之攝取量、化合物在細胞中所待的位置和光毒性表現,可以發現化合 物5b 和8a 具有以下特性:(1)在光動力治療中對癌細胞具有專一性,(2)相對於 methylene blue 具有較佳的光穩定性,(3)光毒性效果與methylene blue 幾乎一致 而遠高於Foscan,(4)超氧化物的產生以提供額外之光毒性。
We introduce a new class of photostable, efficient photosensitizer base on BODIPY derivatives which can be used to detect acid concentration, generate singlet oxygen and super oxide simultaneously under irradiation. Appropriate regulation of the synthesis procedure coupled with cheaper materials, we can facilitate controlling the generation of specifically substituted position of BODIPY derivatives. Biologically evaluate the uptake, localization and phototoxicity in cell lines, we conclude that compounds 5b and 8a are potential selective PDT candidates due to their photodynamic therapy are more efficient in cancer cell more than normal cell without significant dark toxicity. Based on our knowledge, this is very rare for PDT application of BODIPY derivatives. Furthermore, direct comparison of the photodamage efficacy, our compound is better than Foscan and nearly equal to methylene blue. BODIPY offered many superior optical properties. In this study, by observing the color change and fluorescence enhancement of solution , compounds with proton accepted function groups can be used to detect acid concentration in organic solvent and aqueous solution. Besides we have successfully applied BODIPY derivatives for cancer targeting and demonstrated that compound 5b and 8a may be potent tumor-specific photosensitizers for PDT. First, we presented that cheap and convenient synthesis procedure which can be widely applied for the preparation of diversified BODIPY derivatives. Second, biological evolution of the ROS generation and cellular uptake, localization and phototoxicity, therefore, the PDT characteristics of the compound 5b and 8a include (1) target selectivity for the PDT of cancer cells; (2) high photostability than methylene blue; (3) photodamage efficiency is much better than Foscan and nearly equal to MB; (4) supported extra phototoxicity with super oxide generation.
URI: http://hdl.handle.net/11455/3948
其他識別: U0005-2008201313591400
文章連結: http://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-2008201313591400
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