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Toward a novel metal-based chemotherapy against tropical diseases. Part 5. Synthesis and characterization of new Ru(II) and Ru(III) clotrimazole and ketoconazole complexes and evaluation of their activity against Trypanosoma cruzi

Abstract:

The complexes RuCl<inf>3</inf>(CTZ)<inf>3</inf>·2CH<inf>3</inf>OH (1) and RuCl<inf>3</inf>(KTZ)<inf>2</inf>(H<inf>2</inf>O)·2H<inf>2</inf>O (2) were prepared by reaction of RuCl<inf>3</inf>·3H<inf>2</inf>O with CTZ and KTZ, respectively, while RuCl<inf>2</inf>(KTZ)<inf>2</inf> (4) was prepared by reaction of RuCl<inf>2</inf>(CH<inf>3</inf>CN)<inf>4</inf> with KTZ (CTZ = 1-[(2-chlorophenyl)diphenylmethyl-1H-imidazole, and KTZ = cis-1-acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dio xolan-4-yl]methoxy]phenyl]piperazine. All the complexes were characterized by NMR spectroscopy and for the paramagnetic species EPR spectroscopy was also employed. The new compounds were tested for in vitro activity against cultures of epimastigotes of Trypanosoma cruzi, the causative agent of Chagas disease, and compared with RuCl<inf>2</inf>(CTZ)<inf>2</inf> (3) (reported previously) in order to establish some structure-activity correlations. At concentrations of 10<sup>-6</sup> M (DMSO), all the complexes showed higher activity than the parental organic drug against the epimastigote form of the parasite, and Ru(II) complexes seem to be more active than their Ru(III) counterparts for a given nitrogen-donor ligand. © 2000 Elsevier Science B.V.