4-nitroacetophenone-derived thiosemicarbazones and their copper(II) complexes with significant in vitro anti-trypanosomal activity.
N(4)-methyl-4-nitroacetophenone thiosemicarbazone (H4NO(2)Ac4M, 1), N(4),N(4)-dimethyl-4-nitroacetophenone thiosemicarbazone (H4NO(2)Ac4DM, 2) and N(4)-piperidyl-4-nitroacetophenone thiosemicarbazone (H4NO(2)Ac4Pip, 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.
Pérez-Rebolledo
Anayive
A
Departamento de Química, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil.
Teixeira
Letícia R
LR
Batista
Alzir A
AA
Mangrich
Antonio S
AS
Aguirre
Gabriela
G
Cerecetto
Hugo
H
González
Mercedes
M
Hernández
Paola
P
Ferreira
Ana M
AM
Speziali
Nivaldo L
NL
Beraldo
Heloisa
H
D000098:Acetophenones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry; D003300:Copper; D018360:Crystallography, X-Ray; D004563:Electrochemistry; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D066298:In Vitro Techniques; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013882:Thiosemicarbazones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects
D000098:Acetophenones; D002614:Chelating Agents; D013882:Thiosemicarbazones; D014344:Trypanocidal Agents; D003300:Copper