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

N4-Methyl-4-nitroacetophenone thiosemicarbazone (H4NO2Ac4M, 1), N4,N4-dimethyl-4-nitroacetophenone thiosemicarbazone (H4NO2Ac4DM, 2) and N4-piperidyl-4-nitroacetophenone thiosemicarbazone (H4NO2Ac4Pip, 3) and their copper(II) complexes [Cu(4NO2Ac4M)2] (4), [Cu(4NO2Ac4DM)2] (5) and [Cu(4NO2Ac4Pip)2] (6) were tested for their in vitro ability to inhibit the growth of Trypanosoma cruzi epimastigote forms. H4NO2Ac4DM (2), [Cu(4NO2Ac4M)2] (4) and [Cu(4NO2Ac4DM)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.

Graphical abstractN4-Methyl- (H4NO2Ac4M, 1), N4,N4-dimethyl- (H4NO2Ac4DM, 2) and N4-piperidyl-4-nitroacetophenone thiosemicarbazone (H4NO2Ac4Pip, 3) and their copper(II) complexes [Cu(4NO2Ac4M)2] (4), [Cu(4NO2Ac4DM)2] (5) and [Cu(4NO2Ac4Pip)2] (6) were tested for their in vitro ability to inhibit the growth of Trypanosoma cruzi epimastigote forms. H4NO2Ac4DM (2) as well as complexes 4 and 5 proved to be as active as the clinical reference drugs nifurtimox and benznidazol.Figure optionsDownload full-size imageDownload as PowerPoint slide