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 Trypanosomacruzi

The complexes RuCl3(CTZ)(3). 2CH(3)OH (1) and RuCl3(KTZ)(2)(H2O). 2H(2)O (2 ) were prepared by reaction of RuCl3. 3H(2)O with CTZ and KTZ, respectively , while RuCl2(KTZ)(2) (4) was prepared by reaction of RuCl2(CH3CN)(4) 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-dioxola n-4-yl]methoxy]phenyl]piperazine. All the complexes were characterized by N MR spectroscopy and for the paramagnetic species EPR spectroscopy was also employed. The new compounds were tested for in vitro activity against cultu res of epimastigotes of Trypanosoma cruzi, the causative agent of Chagas di sease, and compared with RuCl2(CTZ)(2) (3) (reported previously) in order t o establish some structure-activity correlations. At concentrations of 10(- 6) M (DMSO), all the complexes showed higher activity than the parental org anic drug against the epimastigote form of the parasite, and Ru(II) complex es seem to be more active than their Ru(III) counterparts for a given nitro gen-donor ligand. (C) 2000 Elsevier Science B.V. All rights reserved.