Purpurinimide carbohydrate conjugates: Effect of the position of the carbohydrate moiety in photosensitizing efficacy
Purpurinimide carbohydrate conjugates: Effect of the position of the carbohydrate moiety in photosensitizing efficacy
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DOI：
10.1021/mp060135x
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发表时间：
2007-05-01
影响因子：
4.9
通讯作者：
Pandey, Ravindra K.
中科院分区：
文献类型：
--
作者：
Pandey, Suresh K.;Zheng, Xiang;Pandey, Ravindra K.
在 N-己基-中消紫酰亚胺（一类含有稠合六元酰亚胺环系统的二氢卟酚，λ（max）：700 nm）的不同位置上区域选择性地引入乳糖部分，以研究其存在和位置对光敏功效的影响。由此产生的新颖结构在体外和体内功效上产生了显着差异。在3、8和12位引入乳糖部分的位置异构体中，3-乳糖红紫素-18-N-己酰亚胺产生了最好的功效。与这些类似物相比，在位置17(2)处与酰胺键连接以及在位置13(2)处与带有-CC-键的N-苄基连接的乳糖部分显示出体外/体内光敏性降低。在孵育后 3 小时和 24 小时观察到乳糖缀合物在细胞摄取（RIF 肿瘤细胞）方面存在显着差异。用 purpurinimide 3 位的 β-半乳糖和葡萄糖部分替换乳糖 (Gal beta 1 -> 4Glc) 会增加细胞摄取和体外功效，但会降低体内功效。具有和不具有碳水化合物部分的光敏剂的细胞内定位位点不同。分子模型显示 3- 和 12- 乳糖-紫红酰亚胺类似物与 galectin-1 和 galectin-3 均具有良好的相互作用，但在第 8 位含有乳糖部分的缀合物并未发现明显的相互作用。在乳糖缀合物与游离乳糖的比较 ELISA 研究中，所有碳水化合物-紫紫酰亚胺均显示与两种半乳糖凝集素结合，且各批次半乳糖凝集素之间存在显着差异。
A lactose moiety was regioselectively introduced at various positions of N-hexyl-mesopurpurinimide (a class of chlorin containing a fused six-membered imide ring system, lambda(max): 700 nm) to investigate the effect of its presence and position on photosensitizing efficacy. The resulting novel structures produced a significant difference in in vitro and in vivo efficacy. Among the positional isomers in which the lactose moiety was introduced at positions 3, 8, and 12, the 3-lactose purpurin-18-N-hexylimide produced the best efficacy. Compared to these analogues, the lactose moiety joined with an amide bond at position 17(2), and with an N-benzyl group bearing a -C C- linkage at position 13(2) showed reduced in vitro/in vivo photosensitivity. A noticeable difference between lactose conjugates in cell uptake (RIF tumor cells) was observed at 3 and 24 h postincubation. Replacing the lactose (Gal beta 1 -> 4Glc) with beta-galactose and glucose moieties at position 3 of purpurinimide produced an increase in both cell uptake and in in vitro efficacy, but with reduced in vivo efficacy. Sites of intracellular localization differed among photosensitizers with and without carbohydrate moieties. Molecular modeling shows favorable interactions of 3- and 12-lactose-purpurinimide analogues with both galectin-1 and galectin-3, but clear contributions were not found for the conjugate containing lactose moiety at position 8. In a comparative ELISA study of the lactose conjugates with free lactose, all carbohydrate-purpurinimides showed binding to both galectins with a significant variation between the batches of galectins.