In vitro effect of a new cinnamic acid derivative against the epimastigote form of Trypanosoma cruzi.
An intensive effort has been directed toward finding alternative drugs for treatment of Chagas' disease, caused by Trypanosoma cruzi (T. cruzi), and prophylaxis of blood in endemic areas. The preparation and in vitro evaluation as potential anti-protozoal agent of (2E)-N-(1,3-benzothiazol-2-yl)-3-(2,5-dimethoxyphenyl)-2-propenamide (CAD-1) is presented. The results show that 0.05 mM CAD-1 induced 58.1% of T. cruzi epimastigotes death; mainly by apoptosis. The diminution in the transmembrane mitochondrial electrical potential together with the increase in the intracellular generation/accumulation of reactive oxygen species, suggest the parasites mitochondria as the main target for CAD-1-induced death. The concentration of 0.05 mM CAD-1 is not low enough to consider it as a potent tripanocydal agent. However the novel mechanism that induces T. cruzi death, together with the novelty of its chemical structure, point out CAD-1 as a head group compound that could serve as a template to obtain new, more potent anti-Chagas disease agents.
Pardo Andreu
Gilberto L
GL
Departamento de Investigaciones Biomédicas, Centro de Química Farmacéutica, Ciudad de La Habana, Cuba. gilbertopardo@infomed.sld.cu
Inada
Natalia M
NM
Pellón
Rolando F
RF
Docampo
Maite L
ML
Fascio
Mirta L
ML
D'Accorso
Norma B
NB
Vercesi
Anibal E
AE
D000577:Amides / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D017304:Annexin A5; D052160:Benzothiazoles / Q000302:isolation & purification / Q000494:pharmacology*; D002934:Cinnamates / Q000302:isolation & purification / Q000494:pharmacology*; D004396:Coloring Agents; D004791:Enzyme Inhibitors; D005434:Flow Cytometry; D007202:Indicators and Reagents; D008564:Membrane Potentials / Q000187:drug effects; D011419:Propidium; D017382:Reactive Oxygen Species / Q000378:metabolism; D014344:Trypanocidal Agents / Q000302:isolation & purification / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000378:metabolism
C543348:(2E)-N-(1,3-benzothiazol-2-yl)-3-(2,5-dimethoxyphenyl)-2-propenamide; D000577:Amides; D017304:Annexin A5; D052160:Benzothiazoles; D002934:Cinnamates; D004396:Coloring Agents; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D017382:Reactive Oxygen Species; D014344:Trypanocidal Agents; C029010:cinnamic acid; D011419:Propidium