NDLI: Biotransformations of Anticancer Ruthenium(III) Complexes: An X-Ray Absorption Spectroscopic Study

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Biotransformations of Anticancer Ruthenium(III) Complexes: An X-Ray Absorption Spectroscopic Study

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Biotransformations of Anticancer Ruthenium(III) Complexes: An X-Ray Absorption Spectroscopic Study

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Lim, Zhi Jun Wong, Pok Fai Levina, Aviva Singharay, Anannya Mitra Liu, Mimi Aitken, Jade B. Gwee, Yee Yen Lay, Peter A.
Description	Author Affiliation: Levina A ( School of Chemistry, The University of Sydney, Sydney, NSW 2006, Australia.)
Abstract	An anti-metastatic drug, NAMI-A $((ImH)[Ru^{III}Cl_{4}(Im)(dmso)];$ Im=imidazole, dmso=S-bound dimethylsulfoxide), and a cytotoxic drug, KP1019 $((IndH)[Ru^{III}Cl_{4}(Ind)_{2}];$ Ind=indazole), are two Ru-based anticancer drugs in human clinical trials. Their reactivities under biologically relevant conditions, including aqueous buffers, protein solutions or gels (e.g, albumin, transferrin and collagen), undiluted blood serum, cell-culture medium and human liver (HepG2) cancer cells, were studied by Ru K-edge X-ray absorption spectroscopy (XAS). These XAS data were fitted from linear combinations of spectra of well-characterised Ru compounds. The absence of XAS data from the parent drugs in these fits points to profound changes in the coordination environments of $Ru^{III}.$ The fits point to the presence of $Ru^{IV/III}$ clusters and binding of $Ru^{III}$ to S-donor groups, amine/imine and carboxylato groups of proteins. Cellular uptake of KP1019 is approximately 20-fold higher than that of NAMI-A under the same conditions, but it diminishes drastically after the decomposition of KP1019 in cell-culture media, which indicate that the parent complex is taken in by cells through passive diffusion.
ISSN	09476539
e-ISSN	15213765
Journal	Chemistry - A European Journal
Issue Number	11
Volume Number	19
Language	English
Publisher	Wiley-VCH;ChemPubSoc Europe
Publisher Date	2013-03-11
Publisher Place	Germany
Access Restriction	Open
Subject Keyword	Antineoplastic Agents Metabolism Organometallic Compounds Ruthenium Chemistry Pharmacokinetics Dimethyl Sulfoxide Hep G2 Cells Imidazoles Models, Molecular Molecular Conformation X-Ray Absorption Spectroscopy Research Support, Non-U.S. Gov't
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Catalysis

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