title: Spectroscopic studies of interactions of chondroitin sulfates with cisplatin.
abstract: Complexation of cisplatin (CDDP) and chondroitin sulfate A (CSA) or C (CSC) has been reported to reduce the nephrotoxicity of CDDP. However the mechanism of interaction between CDDP and CSA or CSC was not known. In this study, spectroscopic analyses including NMR were carried out to examine the complexation interactions of CSA and CSC with CDDP. The time-dependent changes in the UV spectra indicate that CSA and CSC effectively complexes with CDDP in aqueous solution and that the reaction occurs subsequent to the hydrolysis of CDDP. The time-dependent change results measured by capillary electrophoresis showed that complexation of chondroitin sulfate (CS) followed first-order reaction kinetics and that the rate of CDDP hydrolysis in the complexation for both CSA and CSC was the same. These results suggested that the mechanism of complexation was a two-step process with monoaqua formation proved to be the first step, which was also the reaction rate controlling step. Moreover, NMR data suggested that the carboxylic and sulfate groups of CS played an important role in its interaction with CDDP.
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
authors.forename: Jing-Shi
authors.initials: JS
authors.lastname: Zhang
authors.forename: Makoto
authors.initials: M
authors.lastname: Anraku
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kadowaki
authors.forename: Teruko
authors.initials: T
authors.lastname: Imai
authors.forename: Ayaka
authors.initials: A
authors.lastname: Suenaga
authors.forename: Akira
authors.initials: A
authors.lastname: Odani
authors.forename: Masaki
authors.initials: M
authors.lastname: Otagiri
mesh_terms: D002809:Chondroitin Sulfates / Q000737:chemistry*; D002945:Cisplatin / Q000737:chemistry*; D004347:Drug Interactions; D019075:Electrophoresis, Capillary; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013056:Spectrophotometry, Ultraviolet
chemical_list: D002809:Chondroitin Sulfates; D002945:Cisplatin