Articulo
Rhenium(I) tricarbonyl compounds of bioactive thiosemicarbazones: Synthesis, characterization and activity against Trypanosoma cruzi
Fecha
2017Registro en:
1150175
WOS:000398881000014
Institución
Resumen
American Trypanosomiasis is a chronic infection discovered and described in 1909 by the Brazilian scientist Carlos Chagas. It is caused by the protozoan parasite Trypanosoma cruzi. Although it affects about 10 million people in Latin America, the current chemotherapy is still inadequate. The discovery of new drugs is urgently needed. Our group is focused on the development of prospective metal-based drugs mainly based on bioactive ligands and pharmacologically interesting metal ions. In this work three new rhenium(I) tricarbonyl compoundsfac-[Re-1(CO)(3)Br(HL)] where HL = 5-nitrofuryl containing thiosemicarbazones were synthesized and fully characterized in solution and in the solid state. The in vitro evaluation of the compounds on T. cruzi trypomastigotes (Dm28c strain) showed that the Re(I) compounds are 8 to 15 times more active than the reference drug Nifurtimox and show a 4 to 17 fold increase in activity in respect to the free (HL) ligands. Obtained compounds also show good selectivity indexes (IC50 endothelial cells (Ea.hy926)/IC50 (T. cruzl) ((Dm28c tripomastigotes))). H-1 NMR and MS studies, performed with time, showed that the fac[Re(C0)3Br(HL)] species convert into the dimers [Re-2(CO)(6)(L)(2)] in solution. Crystal structure of [Re-2(1)(CO)(6)(L2)(2)], the product of complexes' dimerization, was solved. Related to the mechanism of action, the studied compounds do not generate radical oxygen species in the parasite (as 5-nitrofuryl derived thiosemicarbazones do) probably due to the unfavorable nitro reduction potential of the generated dimeric species. On the contrary, the compounds produce a decrease of the oxygen consumption rate of the parasites, maybe inhibiting their mitochondrial respiration. (C) 2017 Elsevier Inc. All rights reserved. Keywords. Author Keywords:fac-Rhenium(I) tricarbonyl compounds; 5-Nitrofuryl derived thiosemicarbazones; Trypanosoma cruzi; Chagas disease; Bioactive ligands . KeyWords Plus:ANTITRYPANOSOMAL AGENTS; CHAGAS-DISEASE; ORGANORUTHENIUM COMPLEXES; CARBONYL-COMPLEXES; PALLADIUM; LIGAND; DRUGS; 5-NITROFURYL; DERIVATIVES; REACTIVITY