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

Abstract

The Ru(III) metronidazole-maltolato and -ethylmaltolato complexes, trans-[RuL 2(metro) 2]CF 3SO 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-1 H-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 3SO 3 ( 4a and 4b) and [Ru(ma) 2(triF5) 2]CF 3SO 3 ( 5) were prepared from the [RuL 2(EtOH) 2]CF 3SO 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.