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

• Published in: European journal of medicinal chemistry Vol. 43; no. 5; pp. 939 - 948
• Main Authors: Pérez-Rebolledo, Anayive, Teixeira, Letícia R., Batista, Alzir A., Mangrich, Antonio S., Aguirre, Gabriela, Cerecetto, Hugo, González, Mercedes, Hernández, Paola, Ferreira, Ana M., Speziali, Nivaldo L., Beraldo, Heloisa
• Format: Journal Article
• Language: English
• Published: PARIS Elsevier Masson SAS 01.05.2008; Elsevier
• Subjects: 4-Nitroacetophenone thiosemicarbazones; Acetophenones - chemical synthesis; Acetophenones - chemistry; Acetophenones - pharmacology; Animals; Anti-trypanosomal activity; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiparasitic agents; Biological and medical sciences; Chelating Agents - chemical synthesis; Chelating Agents - chemistry; Chemistry, Medicinal; Copper; Copper(II) complexes; Crystallography, X-Ray; Electrochemistry; Electron Spin Resonance Spectroscopy; Humans; In Vitro Techniques; Life Sciences & Biomedicine; Macrophages - drug effects; Macrophages - parasitology; Magnetic Resonance Spectroscopy; Medical sciences; Molecular Structure; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Science & Technology; Thiosemicarbazones - chemical synthesis; Thiosemicarbazones - chemistry; Thiosemicarbazones - pharmacology; Trypanocidal Agents - chemical synthesis; Trypanocidal Agents - chemistry; Trypanocidal Agents - pharmacology; Trypanosoma cruzi - drug effects; Anti-trypanosomal activity; Copper(II) complexes; 4-Nitroacetophenone thiosemicarbazones; copper(II) complexes; 4-nitroacetophenone thiosemicarbazones; NITRO RADICAL-ANION; 5-NITROTHIOPHENE-2-CARBOXALDEHYDE SEMICARBAZONE DERIVATIVES; TRYPANOSOMA-CRUZI; ANTIFUNGAL ACTIVITY; ANTIAMEBIC ACTIVITY; ENTAMOEBA-HISTOLYTICA; NICKEL(II); 3-AND 4-ACETYLPYRIDINE; TROPICAL DISEASES; anti-trypanosomal activity; METAL-COMPLEXES; Divalent metal Complexes; Molecular structure; Leukocyte; Toxicity; Cytotoxicity; Cyclic voltammetry; Antiprotozoal agent; Structure activity relation; Copper II Complexes; Chemical synthesis; Kinetoplastida; Human; Protozoa; Organic ligand; Transition metal Complexes; X ray diffraction; In vitro; Trypanosoma cruzi; Electrochemical properties; Epimastigote; Parasiticide; Macrophage; Crystalline structure
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2007.06.020

N 4-Methyl-4-nitroacetophenone thiosemicarbazone (H4NO 2Ac4M, 1), N 4, N 4-dimethyl-4-nitroacetophenone thiosemicarbazone (H4NO 2Ac4DM, 2) and N 4-piperidyl-4-nitroacetophenone thiosemicarbazone (H4NO 2Ac4Pip, 3) and their copper(II) complexes [Cu(4NO 2Ac4M) 2] ( 4), [Cu(4NO 2Ac4DM) 2] ( 5) and [Cu(4NO 2Ac4Pip) 2] ( 6) were tested for their in vitro ability to inhibit the growth of Trypanosoma cruzi epimastigote forms. H4NO 2Ac4DM ( 2), [Cu(4NO 2Ac4M) 2] ( 4) and [Cu(4NO 2Ac4DM) 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. [Display omitted] N 4-Methyl- (H4NO 2Ac4M, 1), N 4, N 4-dimethyl- (H4NO 2Ac4DM, 2) and N 4-piperidyl-4-nitroacetophenone thiosemicarbazone (H4NO 2Ac4Pip, 3) and their copper(II) complexes [Cu(4NO 2Ac4M) 2] ( 4), [Cu(4NO 2Ac4DM) 2] ( 5) and [Cu(4NO 2Ac4Pip) 2] ( 6) were tested for their in vitro ability to inhibit the growth of Trypanosoma cruzi epimastigote forms. H4NO 2Ac4DM ( 2) as well as complexes 4 and 5 proved to be as active as the clinical reference drugs nifurtimox and benznidazol.