Toward a novel metal based chemotherapy against tropical diseases 4. Synthesis and characterization of new metal-clotrimazole complexes and evaluation of their activity against Trypanosoma cruzi

Article abstract of DOI:10.1016/s0020-1693(98)00114-5

The syntheses and characterization of metal imidazole complexes showing activity against Trypanosoma cruzi, the causative agent of Chagas disease, are presented. RuCl₂(CTZ)₂ (2) and RuCl₂(BTZ)₂ (4) were prepared by reaction of RuCl₂(NCCH₃)₄ (1) with the appropriate ligand (CTZ, clotrimazole = 1-[(2-chlorophenyl)diphenylmethyl]-1H-imidazole; BTZ = 1-[(2-bromophenyl) diphenylmethyl] -1H-imidazole). [Ru(bipy) (CTZ)₂] (PF₆)₂ (3) (bipy = 2,2′-bipyridyl) was obtained by reaction of 2 with bipy and NH₄PF₆ in MeCN. Reaction of [RhCl(COD)]₂ with CTZ yielded RhCl(COD)(CTZ) (5) (COD = 1,5-cyclooctadiene), while AuCl₃CTZ (6), K₂[PtCl₄(CTZ)₂] (7) and [Cu(CTZ)₂]PF₆ (8) were obtained by interaction of CTZ with AuCl₃ · HCl, K₂PtCl₄ and [Cu(CH₃CN)₄]PF₆, respectively. All the new complexes were characterized by NMR and other appropriate techniques. X-ray diffraction studies of 4 · 3H₂O, 5 and 6 were also carried out. The structure of 4 · 3H₂O consists of a distorted tetrahedral arrangement of two N atoms from the BTZ ligands and two Cl atoms around the Ru(II) ion; 4 · 3H₂O crystallizes in the orthorhombic space group Pnma (No. 62) with a = 12.818(5), b = 29.115(5), c = 12.040(5) A?, V = 4493.2(8) A?³ and Z = 4. Complex 5 displayed a square planar structure typical for Rh(I) bound to N from CTZ, Cl, and the two C = C bonds of COD; 5 crystallized in the triclinic space group (P(-1) (No.2) with a = 12.407(3), b = 12.876(4), c = 10.069(3) A?, α = 111.59(2)°, β = 107.80(2)°, γ = 103.28(2)°, V = 1313.4(8) A?³ and Z = 2. Complex 6 also displayed a square arrangement of N from CTZ, plus three Cl atoms around the Au(III) ion; 6 crystallized in the monoclinic space group P2₁/n (No. 14) with a = 9.507(1), b = 18.280(4), c = 12.877(1) A?, β = 100.59(1)°, V = 2199.7(5) A?³ and Z = 4. All the new compounds were found to be active against in vitro cultures of Trypanosoma cruzi, following the trend 3 = 7<8a simple model of action of this compound.