Synthesis of a Disulfonated Derivative of Cucurbit[7]uril and Investigations of its Ability to Solubilize Insoluble Drugs.
Synthesis of a Disulfonated Derivative of Cucurbit[7]uril and Investigations of its Ability to Solubilize Insoluble Drugs.
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DOI：
10.1080/10610278.2014.940952
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发表时间：
2015-05-01
影响因子：
3.3
通讯作者：
Isaacs L
中科院分区：
文献类型：
--
作者：
Robinson EL;Zavalij PY;Isaacs L
葫芦[7]脲（CB[7]）目前正在研究作为不溶性药物的增溶剂。我们最近发现，非环状CB[n]型受体，承载磺酸盐增溶基团非常适合于这种应用。在此，我们报道了葫芦[7]脲衍生物（1），其凸面上带有两个磺酸基，我们假设这将是一种上级增溶赋形剂，用于不溶性药物。在使用1进行药物增溶实验之前，我们表明1不自缔合，并且它保留了结合二铵化合物作为CB[7]大小的空腔的常见客体的能力。X射线晶体学显示，1保持CB[7]的关键结构特征，仅在1的赤道和羰基门户处具有轻微的椭圆形变形。不幸的是，1（20 mM）的水溶解度略低于CB[7]（20-30 mM），这限制了其作为不溶性药物的增溶赋形剂的潜力。我们使用两种不同的容器（1和CB[7]）创建了三种药物（喜树碱、阿苯达唑、桂利嗪）增溶的相溶解度图。CB[7]和1对喜树碱和阿苯达唑表现出相当的增溶能力（例如Ka和最大溶解度），但由于1·桂利嗪复合物表现出的低溶解度，1是桂利嗪的较差增溶剂。
Cucurbit[7]uril (CB[7]) is currently being investigated as a solubilizing agent for insoluble drugs. We recently found that acyclic CB[n]-type receptors that bear sulfonate solubilizing groups are well suited for this application. Herein, we report cucurbit[7]uril derivative (1) that bears two sulfonate groups on its convex face that we hypothesized would be a superior solubilizing excipient for insoluble drugs. Before using 1 for drug solubilization experiments we showed that 1 does not self-associate and that it retained its ability to bind to diammonium compounds as common guests for CB[7] sized cavities. X-ray crystallography shows that 1 maintains the key structural features of CB[7] with only minor ellipsoidal deformations at the equator and carbonyl portals of 1. Unfortunately, the aqueous solubility of 1 (20 mM) is slightly lower than CB[7] (20-30 mM) which limits its potential as a solubilizing excipient for insoluble drugs. We created phase solubility diagrams for the solubilization of three drugs (camptothecin, albendazole, cinnarizine) with two different containers (1 and CB[7]). CB[7] and 1 exhibit comparable solubilization abilities (e.g. Ka and maximum solubility) toward camptothecin and albendazole but 1 is an inferior solubilizing agent for cinnarizine because of the low solubility exhibited by the 1•cinnarizine complex.
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影响因子：
8.4
作者：
Dang, Dung T.;Schill, Jurgen;Brunsveld, Luc
通讯作者：
Brunsveld, Luc
影响因子：
15
作者：
Baek, Kangkyun;Yun, Gyeongwon;Kim, Kimoon
通讯作者：
Kim, Kimoon
DOI：
10.1002/anie.199110241
发表时间：
1991-08-01
期刊：
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION IN ENGLISH
影响因子：
--
作者：
CRAM, DJ;TANNER, ME;THOMAS, R
通讯作者：
THOMAS, R
扭曲葫芦[14]uril
影响因子：
16.6
作者：
Cheng, Xiao-Jie;Liang, Li-Li;Tao, Zhu
通讯作者：
Tao, Zhu
影响因子：
16.6
作者：
Dang, Dung T.;Nguyen, Hoang D.;Brunsveld, Luc
通讯作者：
Brunsveld, Luc