Biotransformations of Anticancer Ruthenium(III) Complexes: An X-Ray Absorption Spectroscopic Study
| Autor: | Zhi Jun Lim, Aviva Levina, Mimi Liu, Pok Fai Wong, Peter A. Lay, Yee Yen Gwee, Anannya Mitra Singharay, Jade B. Aitken |
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| Rok vydání: | 2013 |
| Předmět: |
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Molecular Stereochemistry Imine Molecular Conformation chemistry.chemical_element Antineoplastic Agents Medicinal chemistry Ruthenium Catalysis chemistry.chemical_compound Blood serum Organometallic Compounds Humans Imidazole Dimethyl Sulfoxide Indazole X-ray absorption spectroscopy Aqueous solution Organic Chemistry Imidazoles Hep G2 Cells General Chemistry X-Ray Absorption Spectroscopy chemistry Amine gas treating |
| Zdroj: | Chemistry - A European Journal. 19:3609-3619 |
| ISSN: | 0947-6539 |
| DOI: | 10.1002/chem.201203127 |
| Popis: | An anti-metastatic drug, NAMI-A ((ImH)[Ru(III) Cl4 (Im)(dmso)]; Im=imidazole, dmso=S-bound dimethylsulfoxide), and a cytotoxic drug, KP1019 ((IndH)[Ru(III) Cl4 (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. |
| Databáze: | OpenAIRE |
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