| Autor: |
Pereira PML; Graduate Program in Microbiology, Department of Microbiology, State University of Londrina, Londrina 86057-970, Brazil.; Laboratory of Molecular Biology of Microorganisms, Department of Microbiology, State University of Londrina, Londrina 86057-970, Brazil., Fernandes BT; Graduate Program in Microbiology, Department of Microbiology, State University of Londrina, Londrina 86057-970, Brazil.; Laboratory of Molecular Biology of Microorganisms, Department of Microbiology, State University of Londrina, Londrina 86057-970, Brazil., Dos Santos VR; Laboratory of Molecular Biology of Microorganisms, Department of Microbiology, State University of Londrina, Londrina 86057-970, Brazil., Cabral WRC; Graduate Program in Microbiology, Department of Microbiology, State University of Londrina, Londrina 86057-970, Brazil.; Laboratory of Molecular Biology of Microorganisms, Department of Microbiology, State University of Londrina, Londrina 86057-970, Brazil., Lovo-Martins MI; Laboratory of Experimental Immunopathology, Department of Immunology, Parasitology and General Pathology, State University of Londrina, Londrina 86057-970, Brazil., Alonso L; Institute of Physics, Federal University of Goiás, Goiania 74690-900, Brazil., Lancheros CAC; Center for Human, Biological, Social and Educational Sciences, State University of Paraná, Paranagua 83203-560, Brazil., de Paula JC; Department of Parasitology, University of Granada, 18071 Granada, Spain., Camargo PG; Laboratory of Medicinal Molecules Synthesis, Department of Chemistry, State University of Londrina, Londrina 86057-970, Brazil., Suzukawa HT; Graduate Program in Microbiology, Department of Microbiology, State University of Londrina, Londrina 86057-970, Brazil.; Laboratory of Molecular Biology of Microorganisms, Department of Microbiology, State University of Londrina, Londrina 86057-970, Brazil., Alonso A; Institute of Physics, Federal University of Goiás, Goiania 74690-900, Brazil., Macedo F Jr; Laboratory of Medicinal Molecules Synthesis, Department of Chemistry, State University of Londrina, Londrina 86057-970, Brazil., Nakamura CV; Laboratory of Technological Innovation in the Development of Drugs and Cosmetics, Department of Basic Health Sciences, State University of Maringá, Maringa 87020-900, Brazil., Tavares ER; Laboratory of Molecular Biology of Microorganisms, Department of Microbiology, State University of Londrina, Londrina 86057-970, Brazil., de Lima Ferreira Bispo M; Laboratory of Medicinal Molecules Synthesis, Department of Chemistry, State University of Londrina, Londrina 86057-970, Brazil., Yamauchi LM; Graduate Program in Microbiology, Department of Microbiology, State University of Londrina, Londrina 86057-970, Brazil.; Laboratory of Molecular Biology of Microorganisms, Department of Microbiology, State University of Londrina, Londrina 86057-970, Brazil., Pinge-Filho P; Graduate Program in Microbiology, Department of Microbiology, State University of Londrina, Londrina 86057-970, Brazil.; Laboratory of Experimental Immunopathology, Department of Immunology, Parasitology and General Pathology, State University of Londrina, Londrina 86057-970, Brazil., Yamada-Ogatta SF; Graduate Program in Microbiology, Department of Microbiology, State University of Londrina, Londrina 86057-970, Brazil.; Laboratory of Molecular Biology of Microorganisms, Department of Microbiology, State University of Londrina, Londrina 86057-970, Brazil. |
| Abstrakt: |
For decades, only two nitroheterocyclic drugs have been used as therapeutic agents for Chagas disease. However, these drugs present limited effectiveness during the chronic phase, possess unfavorable pharmacokinetic properties, and induce severe adverse effects, resulting in low treatment adherence. A previous study reported that N -(cyclohexylcarbamothioyl) benzamide ( BTU-1 ), N -( tert -butylcarbamothioyl) benzamide ( BTU-2 ), and (4-bromo- N -(3-nitrophenyl) carbamothioyl benzamide ( BTU-3 ) present selective antiprotozoal activity against all developmental forms of Trypanosoma cruzi Y strain. In this study, we investigated the mechanism of action of these compounds through microscopy and biochemical analyses. Transmission electron microscopy analysis showed nuclear disorganization, changes in the plasma membrane with the appearance of blebs and extracellular arrangements, intense vacuolization, mitochondrial swelling, and formation of myelin-like structures. Biochemical results showed changes in the mitochondrial membrane potential, reactive oxygen species content, lipid peroxidation, and plasma membrane fluidity. In addition, the formation of autophagic vacuoles was observed. These findings indicate that BTU-1 , BTU-2, and BTU-3 induced profound morphological, ultrastructural, and biochemical alterations in epimastigote forms, triggering an autophagic-dependent cell death pathway. |
