title: Complexation of fisetin with novel cyclosophoroase dimer to improve solubility and bioavailability.
abstract: Rhizobium species produce cyclosophoraose (Cys), which is an unbranched cyclic β-(1,2)-glucan. We synthesized novel cationic cyclosophoraose dimer (Cys dimer) and its structure was confirmed via NMR spectroscopy and MALDI-TOF mass spectrometry analysis. In this study, we investigated the complexation of hardly soluble drug fisetin (3,3',4',7-tetrahydroxyflavone) with Cys dimer to improve the solubility of fisetin, and its solubility was increased up to 6.5-fold. The solubility of fisetin with Cys dimer showed 2.4-fold better than with β-cyclodextrin. The fisetin-Cys dimer complex was characterized by using, phase solubility diagram, 2D NMR, FT-IR spectroscopy, SEM, DSC analysis and molecular modeling. Through the molecular docking simulations, complexation ability of fisetin with host molecules were in the following order: Cys dimer>Cys monomer>β-CD. The fisetin-Cys dimer complex showed also higher cytotoxicity to HeLa cells than free fisetin, indicating that the Cys dimer to improve bioavailability of fisetin.
authors.affiliation: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center & Institute for Ubiquitous Information Technology and Applications (CBRU), Konkuk University, Seoul 143-701, South Korea.
authors.forename: Daham
authors.initials: D
authors.lastname: Jeong
authors.forename: Jae Min
authors.initials: JM
authors.lastname: Choi
authors.forename: Youngjin
authors.initials: Y
authors.lastname: Choi
authors.forename: Karpjoo
authors.initials: K
authors.lastname: Jeong
authors.forename: Eunae
authors.initials: E
authors.lastname: Cho
authors.forename: Seunho
authors.initials: S
authors.lastname: Jung
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D019281:Dimerization; D005419:Flavonoids / Q000737:chemistry* / Q000633:toxicity; D044948:Flavonols; D005936:Glucans / Q000737:chemistry* / Q000633:toxicity; D006367:HeLa Cells; D006801:Humans; D012231:Rhizobium / Q000378:metabolism; D012995:Solubility; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D005419:Flavonoids; D044948:Flavonols; D005936:Glucans; D047392:beta-Cyclodextrins; C031215:betadex; C017875:fisetin