Water-Soluble Glucosyl Pyrene Photosensitizers: An Intramolecularly Synthesized 2-C-Glucoside and an O-Glucoside
Water-Soluble Glucosyl Pyrene Photosensitizers: An Intramolecularly Synthesized 2-C-Glucoside and an O-Glucoside
复制标题
DOI：
10.1021/acs.joc.8b02066
复制
发表时间：
2018-11-16
影响因子：
3.6
通讯作者：
Yuasa, Hideya
中科院分区：
文献类型：
--
作者：
Kanamori, Takashi;Matsuyama, Akira;Yuasa, Hideya
用于光动力疗法（PDT）的常用光敏剂具有相对大的分子量，从而引起光性皮肤病。在这方面，低分子量的芘可能是一个有效的光敏剂，除了其极端的疏水性。为了解决芘的不溶性问题，我们通过栓系C-葡萄糖基化合成了1-羧基芘-2-基C-葡萄糖苷4，通过简单的O-葡萄糖基化合成了1-芘甲基O-葡萄糖苷5。化合物4和5显示出适度的水溶解度，分别为72和47 μ g/mL。而化合物4在pH 3下部分地经历环化反应，在24小时后以31%的产率得到相应的δ-戊内酯15 b，其在pH 5-9下稳定至少一周。4和5的产生O-1（2）的光敏性足以应用于PDT。虽然化合物5被HeLa细胞摄取并显示出良好的PDT活性，但化合物4既没有显示出足够的细胞摄取也没有显示出PDT效果。化合物4和5与伴刀豆球蛋白A的结合模式分别为特异性和非特异性。这些结果表明，化合物4和5在作为口服药物的可接受范围内，并且分别可以是α-葡萄糖/甘露糖受体的荧光成像探针和PDT的光敏剂。
Prevalent photosensitizing agents for photo dynamic therapy (PDT) suffer from their relatively large molecular weights causing photodermatosis. In this regard, low molecular weight pyrene could be an efficient photosensitizer except for its extreme hydrophobicity. To tackle the insolubility of pyrene, we synthesized 1-carboxypyren-2-yl C-glucoside 4 by a tethered C-glucosylation and 1-pyrenylmethyl O-glucoside 5 by a simple O-glucosylation. Compounds 4 and 5 showed modest water solubilities of 72 and 47 mu g/mL, respectively. Whereas compound 4 partially underwent a cyclization reaction at pH 3 to give the corresponding delta-valerolactone 15b in 31% yield after 24 h, it is stable at pH 5-9 for at least a week. The O-1(2)-producing photosensitizabilities of 4 and 5 were sufficient to apply to PDT. Although compound 5 was uptaken by HeLa cells and showed a good PDT activity, compound 4 showed neither a sufficient cell uptake nor PDT effect. The binding modes of compounds 4 and 5 to concanavalin A were specific and unspecific, respectively. These results demonstrate that compounds 4 and 5 are within a pharmacologically acceptable range as oral drugs and could be a fluorescence imaging probe for alpha-glucose/mannose receptors and a photosensitizing agent for PDT, respectively.