| Synthesis, characterization, and reaction pathways for the formation of a GMP adduct of a cytotoxic thiocyanato ruthenium arene complex. | |
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MedLine Citation:
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PMID: 19499253 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The organoruthenium complex [(eta(6)-hmb)Ru(en)(Cl)][PF6] (hmb is hexamethylbenzene, en is ethylenediamine) undergoes facile aquation and then reacts with KSCN in unbuffered solution to give the S-coordinated thiocyanato product [(eta(6)-hmb)Ru(en)(S-SCN)]+ which slowly converts to the thermodynamically favored N-bound complex [(eta(6)-hmb)Ru(en)(N-NCS)]+ (1+). Complex 1 was synthesized and characterized by X-ray crystallography and mass spectrometry. Despite its lack of hydrolysis over 24 h, complex 1 exhibits moderate cytotoxicity (IC(50) 24 microM) towards the human ovarian cancer cell line A2780, comparable with that of the chlorido analogue which is thought to be activated (towards potential target DNA) via a rapid aquation (Wang et. al. in Proc Natl Acad Sci USA 102:18269-18274, 2005). Detailed kinetic studies suggest that complex 1 binds to guanosine 5'-monophosphate (GMP) through direct N7 substitution of the N-bound SCN ligand. In the presence of a high concentration of chloride (104 mM), however, complex 1 may bind partly to GMP via Cl substitution. |
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Authors:
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Fuyi Wang; Abraha Habtemariam; Erwin P L van der Geer; Robert J Deeth; Robert Gould; Simon Parsons; Peter J Sadler |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-06-05 |
Journal Detail:
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Title: Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry Volume: 14 ISSN: 1432-1327 ISO Abbreviation: J. Biol. Inorg. Chem. Publication Date: 2009 Sep |
Date Detail:
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Created Date: 2009-09-17 Completed Date: 2009-12-29 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9616326 Medline TA: J Biol Inorg Chem Country: Germany |
Other Details:
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Languages: eng Pagination: 1065-76 Citation Subset: IM |
Affiliation:
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Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, 100190 Beijing, China. fuyi.wang@iccas.ac.cn |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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5'-Guanylic Acid
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chemistry* Antineoplastic Agents / chemical synthesis*, chemistry, pharmacology Cell Line, Tumor Chromatography, High Pressure Liquid Computational Biology Crystallography, X-Ray Humans Hydrolysis Inhibitory Concentration 50 Kinetics Models, Molecular Molecular Structure Organometallic Compounds / chemical synthesis, chemistry*, pharmacology Ruthenium / chemistry* Spectrometry, Mass, Electrospray Ionization Spectrophotometry Thiocyanates / chemical synthesis, chemistry*, pharmacology Time Factors |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Organometallic Compounds; 0/Thiocyanates; 7440-18-8/Ruthenium; 85-32-5/5'-Guanylic Acid |
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