Hirohara Shiho, Obata Makoto, Alitomo Hiroki, Sharyo Kohei, Ando Tsuyoshi, Tanihara Masao, Yano Shigenobu
Graduate School of Materials Science, Nara Institute of Science and Technology, Ikoma, Nara, Japan.
J Photochem Photobiol B. 2009 Oct 6;97(1):22-33. doi: 10.1016/j.jphotobiol.2009.07.007. Epub 2009 Jul 24.
Eight S-glycosylated 5,10,15,20-tetrakis(tetrafluorophenyl)porphyrins (1a', 1b', 1a and 1b (a: S-glucosylated, b: S-galactosylated)) and their 1,3-dipolar cycloadducts, i.e. chlorins 2a', 2b', 2a and 2b were prepared by nucleophilic substitution of the pentafluorophenyl groups with S-glycoside. These photosensitizers were characterized by (1)H, (13)C and (19)F NMR spectroscopies and elemental analysis. The photocytotoxicity of the S-glycosylated photosensitizers and the parent porphyrin (1) and chlorin (2) was examined in HeLa cells. Photosensitizers 1, 2, 1a', 1b', 2a' and 2b' showed no significant photocytotoxicity at the concentration of 0.5microM, while the deprotected photosensitizers 1a, 1b, 2a and 2b were photocytotoxic. The strong inhibition by sodium azide of the photocytotoxicity of these photosensitizers suggested that (1)O(2) is the main mediator. The S-glucosylated photosensitizers 1a and 2a showed higher photocytotoxicity than S-galactosylated 1b and 2b, respectively. The cellular uptake of 1a and 2a increased up to 24h, while that of 1b and 2b was saturated by 12h.
通过用S-糖苷对五氟苯基进行亲核取代反应，制备了8种S-糖基化的5,10,15,20-四（四氟苯基）卟啉（1a'、1b'、1a和1b（a：S-葡萄糖基化，b：S-半乳糖基化））及其1,3-偶极环加成物，即二氢卟酚2a'、2b'、2a和2b。这些光敏剂通过¹H、¹³C和¹⁹F核磁共振光谱以及元素分析进行表征。在HeLa细胞中检测了S-糖基化光敏剂以及母体卟啉（1）和二氢卟酚（2）的光细胞毒性。光敏剂1、2、1a'、1b'、2a'和2b'在0.5μM浓度下未显示出明显的光细胞毒性，而脱保护的光敏剂1a、1b、2a和2b具有光细胞毒性。叠氮化钠对这些光敏剂光细胞毒性的强烈抑制表明单线态氧是主要介质。S-葡萄糖基化的光敏剂1a和2a分别比S-半乳糖基化的1b和2b表现出更高的光细胞毒性。1a和2a的细胞摄取在24小时内增加，而1b和2b的细胞摄取在12小时时达到饱和。
