Spectroscopic studies of interactions of chondroitin sulfates with cisplatin |
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Authors: | Zhang Jing-Shi Anraku Makoto Kadowaki Daisuke Imai Teruko Suenaga Ayaka Odani Akira Otagiri Masaki |
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Institution: | aDepartment of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan;bFaculty of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0082, Japan;cFaculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Fukuyama 729-0292, Japan;dDivision of Pharmaceutical Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa 920-1192, Japan |
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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. |
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Keywords: | Cisplatin Chondroitin sulfate Interaction Capillary electrophoresis Spectroscopy NMR |
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