209979-94-2

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• 23593-75-1 clotrimazole 
• 13682-61-6 potassium tetrachloroaurate(III) 

Relevant academic research and scientific papers

Clinically used antifungal azoles as ligands for gold(iii) complexes: the influence of the Au(iii) ion on the antimicrobial activity of the complex

In a search for novel antimicrobial metal-based therapeutic agents, mononuclear gold(iii) complexes 1-7 of the general formula [AuCl3(azole)], where azole stands for imidazole (im, 1), 1-isopropylimidazole (ipim, 2), 1-phenylimidazole (phim, 3), clotrimazole (ctz, 4), econazole (ecz, 5), tioconazole (tcz, 6) and voriconazole (vcz, 7) were synthesized, characterized and biologically evaluated. In all complexes, the corresponding azole ligand is monodentately coordinated to the Au(iii) via the imidazole or triazole nitrogen atom, while the remaining coordination sites are occupied by chloride anions leading to the square-planar arrangement. In vitro antimicrobial assays showed that the complexation of inactive azoles, imidazole, 1-isopropylimidazole and 1-phenylimidazole, to the Au(iii) ion led to complexes 1-3, respectively, with moderate activity against the investigated strains and low cytotoxicity on the human normal lung fibroblast cell line (MRC-5). Moreover, gold(iii) complexes 4-7 with clinically used antifungal agents clotrimazole, econazole, tioconazole and voriconazole, respectively, have, in most cases, enhanced antimicrobial effectiveness relative to the corresponding azoles, with the best improvement achieved after complexation of tioconazole (6) and voriconazole (7). The complexes 4-7 and the corresponding antifungal azoles inhibited the growth of dermatophyte Microsporum canis at 50 and 25 μg mL?1. Gold(iii) complexes 1-3 significantly reduced the amount of ergosterol in the cell membrane of Candida albicans at the subinhibitory concentration of 0.5 × MIC (minimal inhibitory concentration), while the corresponding imidazole ligands did not significantly affect the ergosterol content, indicating that the mechanism of action of the gold(iii)-azole complexes is associated with inhibition of ergosterol biosynthesis. Finally, complexes 5 and 6 significantly reduced the production of pyocyanin, a virulence factor in Pseudomonas aeruginosa controlled by quorum sensing, and increased cell survival after exposure to this bacterium. These findings could be of importance for the development of novel gold(iii)-based antivirulence therapeutic agents that attenuate virulence without pronounced effect on the growth of the pathogens, offering a lower risk for resistance development.

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

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 = 7a simple model of action of this compound.