Coordination of nitro-thiosemicarbazones to ruthenium(II) as a strategy for anti-trypanosomal activity improvement

Complexes [RuCl(H4NO2Fo4M)(bipy)(dppb)]PF6 (1), [RuCl(H4NO2Fo4M)(Mebipy)(dppb)]PF6 (2), [RuCl(H4NO2Fo4M)(phen)(dppb)]PF6 (3), [RuCl(H4NO2Ac4M)(bipy)(dppb)]PF6 (4), [RuCl(H4NO2Ac4M)(Mebipy)(dppb)]PF6 (5) and [RuCl(H4NO2Ac4M)(phen)(dppb)]PF6 (6) with N4-methyl-4-nitrobenzaldehyde thiosemicarbazone (H4NO2Fo4M) and N4-methyl-4-nitroacetophenone thiosemicarbazone (H4NO2Ac4M) were obtained from [RuCl2(bipy)(dppb)], [RuCl2(Mebipy)(dppb)], and [RuCl2(phen)(dppb)], (dppb = 1,4-bis(diphenylphospine)butane; bipy = 2,2′-bipyridine; Mebipy = 4,4′-dimethyl-2,2′-bipyridine; phen = 1,10-phenanthroline). In all cases the thiosemicarbazone is attached to the metal center through the sulfur atom.Complexes (1–6), together with the corresponding ligands and the Ru precursors were evaluated for their ability to in vitro suppress the growth of Trypanosoma cruzi. All complexes were more active than their corresponding ligands and precursors. Complexes (1–3) and (5) revealed to be the most active among all studied compounds with ID50 = 0.6–0.8 μM.In all cases the association of the thiosemicarbazone with ruthenium, dppb and bipyridine or phenanthroline in one same complex proved to be an excellent strategy for activity improvement.

The association of a nitro-thiosemicarbazone with ruthenium(II), dppb = 1,4-bis(diphenylphospine)butane and bipyridine (bipy) or phenanthroline (phen) in one same complex proved to be an excellent strategy of anti-T. cruzi activity improvement.Figure optionsDownload as PowerPoint slide