4-Nitroacetophenone-derived thiosemicarbazones and their copper(II) complexes with significant in vitro anti-trypanosomal activity

N-4-Methyl-4-nitroacetophenone thiosemicarbazone (H4NO2Ac4M, 1), N-4,N-4-dimethyl-4-nitroacetophenone thiosemicarbazone (H4NO2 Ac4DM, 2) and N4-piperidyl-4-nitroacetophenone thiosemicarbazone (H(4)NO(2)Ac(4)Pip, 3) and their copper(II) complexes [Cu(4NO(2)Ac4M)(2)] (4), [Cu(4NO(2)Ac4DM)(2)] (5) and [Cu(4NO(2)Ac4Pip)(2)] (6) were tested for their in vitro ability to inhibit the growth of Trypanosoma cruzi epimastigote forms. H4NO(2)Ac4DM (2), [Cu(4NO(2)Ac4M)(2)] (4) and [Cu(4NO(2)Ac4DM)(2)] (5) proved to be as active as the clinical reference drugs nifurtimox and benznidazol. Taking into consideration the serious side effects and the poor efficacy of the reference drugs, as well as the appearance of resistance during treatment, the studied compounds could constitute a new class of anti-trypanosomal drug candidates. (C) 2007 Elsevier Masson SAS. All rights reserved.