In vitro antiparasitic activity of new thiosemicarbazones in strains of Trypanosoma cruzi

• Published in: European journal of medicinal chemistry Vol. 87; pp. 23 - 29
• Main Authors: Moreno-Rodríguez, Adriana, Salazar-Schettino, Paz María, Bautista, Juan Luis, Hernández-Luis, Francisco, Torrens, Hugo, Guevara-Gómez, Yolanda, Pina-Canseco, Socorro, Torres, Martha Bucio, Cabrera-Bravo, Margarita, Martinez, Cesar Mendoza, Pérez-Campos, Eduardo
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 24-11-2014
• Subjects: Apoptosis; Apoptosis - drug effects; Blood Platelets - drug effects; Blood Platelets - parasitology; Cells, Cultured; Chagas Disease - drug therapy; Flow Cytometry; Humans; In Vitro Techniques; Molecular Structure; Monocytes - drug effects; Monocytes - parasitology; Platelet activation; Platelet Activation - drug effects; Structure–activity relationship; Thiosemicarbazones; Thiosemicarbazones - chemistry; Trypanocidal activity; Trypanocidal Agents - chemistry; Trypanocidal Agents - pharmacology; Trypanosoma cruzi - drug effects; Platelet activation; Trypanocidal activity; Thiosemicarbazones; Structure–activity relationship; Apoptosis
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2014.09.027

In this study thiosemicarbazones derivatives of 5-[(trifluoromethyl)phenylthio]-2-furaldehyde were synthesized and evaluated in terms of their efficiency in challenging the growth of epimastigote forms of Trypanosoma cruzi, the etiological agent of Chagas' disease. A number of compounds were synthesized from 5-bromo-2-furfuraldehyde using nucleophilic aromatic substitution, with a series of trifluoromethyl thiolates, followed by condensation reactions with thiosemicarbazide. Their molecular structures were determined by 1H, 13C and 19F NMR, MS and IR spectroscopy. When tested with T. cruzi, they showed a stronger reaction, similar to nifurtimox and benznidazole, with the 5-[nitro-4-(trifluoromethyl)phenyltio]-2-furaldehyde thiosemicarbazone (compound 4) showing the highest antiparasitic activity. This improved activity may be explained due to the nitro group present in the molecule, which potentiates its activity. The thiosemicarbazone derivatives in this study showed no apoptosis in platelets or monocytes, nor did they induce platelet activation. The trypanocidal activity of these substances represents a good starting point for a medicinal chemistry program aimed at therapy for Chagas' disease.
New thiosemicarbazone derivatives with trypanocidal activity were synthesized which may act as a potential agent in Chagas' disease. [Display omitted]
•New thiosemicarbazones with trypanocidal activity were synthesized.•These produced no apoptosis in platelets or monocytes, nor in platelet activation.•Of the five thiosemicarbazones, only one has significant activity in Trypanosoma cruzi.