Hirohara Shiho, Obata Makoto, Saito Atsuhiro, Ogata Shin-ichi, Ohtsuki Chikara, Higashida Suguru, Ogura Shun-ichiro, Okura Ichiro, Sugai Yuko, Mikata Yuji, Tanihara Masao, Yano Shigenobu
Division of Material Science, Graduate School of Human Culture, Nara Women's University, Nara 630-8560, Japan.
Photochem Photobiol. 2004 Sep-Oct;80(2):301-8. doi: 10.1562/2004-03-07-RA-103.
Thirty-two glycoconjugated porphyrins were synthesized by a modification of Lindsey method in the presence of Zn(OAc)(2).2H(2)O as a template. The Zn(2+) ion template strategy improved the yield about three-fold in the case of meta-substituted tetraphenylporphyrins. In addition, free-base porphyrins were obtained almost quantitatively by demetalation with 4 M HCl. Sixteen deacetylated glycoconjugated porphyrins were tested as candidate photodynamic therapy (PDT) drugs using HeLa cells. Most of the deacetylated glycoconjugated porphyrins showed higher cellular uptake than tetraphenylporphyrin tetrasulfonic acid (TPPS), and 5,10,15,20-tetrakis[4-(beta-D-arabinopyranosyloxy)phenyl]porphyrin (p-5d) in particular showed 18.5-fold higher uptake than TPPS. The photocytotoxicity of 5,10,15,20-tetrakis[4-(beta-D-glucopyranosyloxy)phenyl]porphyrin (p-5a), p-5d and TPPS was examined with HeLa cells, using a light dose of 16 J/cm(2). These photosensitizers had no cytotoxicity in the dark, but their photocytotoxicity increased in the order of TPPS < p-5a < p-5d. These results suggest p-5d is a good candidate for a PDT drug.
在Zn(OAc)(2).2H(2)O作为模板的情况下，通过对Lindsey方法进行改进合成了32种糖缀合卟啉。对于间位取代的四苯基卟啉，Zn(2+)离子模板策略使产率提高了约三倍。此外，用4 M HCl脱金属几乎定量地得到了游离碱卟啉。使用HeLa细胞对16种脱乙酰化糖缀合卟啉作为光动力疗法（PDT）候选药物进行了测试。大多数脱乙酰化糖缀合卟啉显示出比四苯基卟啉四磺酸（TPPS）更高的细胞摄取率，特别是5,10,15,20-四[4-(β-D-阿拉伯吡喃糖氧基)苯基]卟啉（p-5d）的摄取率比TPPS高18.5倍。使用16 J/cm(2)的光剂量，用HeLa细胞检测了5,10,15,20-四[4-(β-D-吡喃葡萄糖氧基)苯基]卟啉（p-5a）、p-5d和TPPS的光细胞毒性。这些光敏剂在黑暗中没有细胞毒性，但它们的光细胞毒性按TPPS < p-5a < p-5d的顺序增加。这些结果表明p-5d是一种很好的PDT药物候选物。
