A novel β-cyclodextrin-rhein conjugate for improving the water solubility and bioavailability of rhein. (April 2020)

• Record Type: Journal Article
• Authors: Wang, Jingjing; Qian, Ying; Qian, Chen; Shi, Fanli; Yao, Jingyuan; Bi, Xiaolin; Chen, Zhipeng
• Is Part Of: Carbohydrate research. Volume 490(2020)
• Publication Date: 2020-04
• Subjects: Cyclodextrin derivative -- Rhein -- Biological activity; Carbohydrates -- Periodicals; Chemistry, Organic -- Periodicals; Biochemistry -- Periodicals; Carbohydrates -- Periodicals; Chimie organique -- Périodiques; Glucides -- Périodiques; Biochemistry; Carbohydrates; Chemistry, Organic; Periodicals; Electronic journals; 507.78
• DOI: 10.1016/j.carres.2020.107958
• Languages: English
• ISSNs: 0008-6215

Abstract

Abstract: 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 1 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. Graphical abstract: 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 1H 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. Image 1 Highlights: Rhein is a potential antitumor agent, but the poor water-solubility restricts its clinical applicability. 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 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.