Ruthenium(III) maltolato-nitroimidazole complexes: synthesis and biological activity.

Abstract

The Ru(III) metronidazole-maltolato and -ethylmaltolato complexes, trans-[RuL(2)(metro)(2)]CF(3)SO(3) (L=ma (1a) or etma (1b)), have been synthesized and tested for potential anti-tumour activity against the human breast cancer cell line MDA-MB-435S using a so-called MTT assay in phosphate-buffered saline; ma=3-hydroxy-2-methylpyran-4-onato, etma=2-ethyl-3-hydroxypyran-4-onato, metro=2-methyl-5-nitro-1H-imidazole-1-ethanol (metronidazole); MTT=3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. The complexes exhibit lower IC(50) values than our previously reported Ru(III) tris-maltolato and -ethylmaltolato complexes [D.C. Kennedy, A. Wu, B.O. Patrick, B.R. James, Inorg. Chem. 44 (2005) 6529-6535]. An improved synthetic route to the 2-nitroimidazole EF5 (2-(2-nitro-1-H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide) is reported, as well as a related synthesis of a 3-nitro-1,2,4-triazole derivative of EF5, triF5 (2-(3-nitro-1-H-triazol-1-yl)-N-(2,2,3,3,3- pentafluoropropyl)acetamide). The complexes [RuL(2)(EF5)(2)]CF(3)SO(3) (4a and 4b) and [Ru(ma)(2)(triF5)(2)]CF(3)SO(3) (5) were prepared from the [RuL(2)(EtOH)(2)]CF(3)SO(3) complexes (3a and 3b); IC(50) values for 3-5 are high. Data on the uptake of Ru by the cells are also reported. The complexes were characterized generally by all or some of the following methods: elemental analyses, NMR, IR and mass spectroscopies, conductivity, and cyclic voltammetry; complexes 1a and 1b were also analyzed by X-ray crystallography.

• Authors: David C Kennedy, Adam Wu, Brian O Patrick, Brian R James
• Journal: Journal of inorganic biochemistry (J Inorg Biochem) Vol. 100 Issue 12 Pg. 1974-82 (Dec 2006) ISSN: 0162-0134 [Print] United States
• PMID: 16938347 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Imidazoles
• Organometallic Compounds
• Ruthenium(III) maltolato-nitroimidazole

Topics

• Antineoplastic Agents (chemical synthesis, pharmacology)
• Cell Line, Tumor
• Crystallography, X-Ray
• Drug Screening Assays, Antitumor
• Humans
• Imidazoles (chemical synthesis, pharmacology)
• Magnetic Resonance Spectroscopy
• Organometallic Compounds (chemical synthesis, pharmacology)