College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, China.
College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, China.
Carbohydr Res. 2020 Apr;490:107958. doi: 10.1016/j.carres.2020.107958. Epub 2020 Feb 19.
Rhein is a potential antitumor agent, but the poor water-solubility restricts its clinical applicability. β-cyclodextrin-drug conjugates provide a possibility to improve the water-solubility of rhein and thereby enhance its bioavailability. A novel β-cyclodextrin-rhein conjugate (β-CD-RH) was synthesized by covalently link β-cyclodextrin with rhein through a 1,8-diamino-3,6-dioxaoctane linker. The structure of β-CD-RH was characterized by H NMR, FT-IR, Maldi-tof MS etc. The inclusion style of β-CD-RH in water was detected by 2D NMR. The 2D ROESY spectrum provided details of the rhein moiety encapsulated in the β-CD cavity. The water-solubility of β-CD-RH is up to 3.24 μmol/mL β-CD-RH exhibited higher cytotoxicity than rhein and rhein/β-CD mixture against Hela cells. Our work provides a new way for the preparation of novel β-CD-drug conjugate.
大黄酸是一种有潜力的抗肿瘤药物，但较差的水溶性限制了其临床应用。β-环糊精-药物缀合物为提高大黄酸的水溶性，从而提高其生物利用度提供了可能。通过 1,8-二氨基-3,6-二氧辛烷连接子将β-环糊精与大黄酸共价连接，合成了一种新型的β-环糊精-大黄酸缀合物（β-CD-RH）。通过 1 H NMR、FT-IR、Maldi-tof MS 等方法对 β-CD-RH 的结构进行了表征。通过二维 NMR 检测了β-CD-RH 在水中的包合方式。二维 ROESY 谱图提供了大黄酸部分被包裹在β-CD 腔中的详细信息。β-CD-RH 的水溶性高达 3.24μmol/mL，β-CD-RH 对 Hela 细胞的细胞毒性高于大黄酸和大黄酸/β-CD 混合物。我们的工作为新型β-CD-药物缀合物的制备提供了一种新方法。
