| Author | Sangenito, Leandro S. | |
| Author | Rodrigues, Hallana D. | |
| Author | Santiago, Simone O. | |
| Author | Bombaça, Ana Cristina S. | |
| Author | Menna-Barreto, Rubem F.S. | |
| Author | Reddy, Andrew | |
| Author | Branquinha, Marta H. | |
| Author | Velasco-Torrijos, Trinidad | |
| Author | Santos, André L.S. | |
| Access date | 2021-11-12T15:05:15Z | |
| Available date | 2021-11-12T15:05:15Z | |
| Document date | 2021 | |
| Citation | SANGENITO, Leandro S. et al. In vitro effects of bis(N-[4-(hydroxyphenyl)methyl]-2-pyridinemethamine) zinc perchlorate monohydrate 4 on the physiology and interaction process of Leishmania amazonensis. Parasitology International, v. 84, 102376, p. 1-6, May 2021. | pt_BR |
| ISSN | 1383-5769 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/49816 | |
| Language | eng | pt_BR |
| Publisher | Elsevier | pt_BR |
| Rights | restricted access | |
| Subject in Portuguese | Leishmania amazonensis | pt_BR |
| Subject in Portuguese | Aminopiridil | pt_BR |
| Subject in Portuguese | Quelante de metal | pt_BR |
| Subject in Portuguese | Complexo de zinco | pt_BR |
| Subject in Portuguese | Ação anti-Leishmania | pt_BR |
| Title | In vitro effects of bis(N-[4-(hydroxyphenyl)methyl]-2-pyridinemethamine) zinc perchlorate monohydrate 4 on the physiology and interaction process of Leishmania amazonensis | pt_BR |
| Type | Article | |
| DOI | 10.1016/j.parint.2021.102376 | |
| Abstract | Despite the high morbidity, mortality and socio-economic impact, few therapeutic options are available for this
disease. To make matters worse, the available molecules have several limitations such as limited efficacy, high
cost, side effects and increased resistance. In this context, our group previously synthesized new compounds with
anti-leishmania potential being the bis(N-[4-(hydroxyphenyl)methyl]-2-pyridinemethamine)zinc perchlorate
monohydrate 4 (complex 4) the most promising one. Therefore, this present work revealed some morphological
and physiological changes promoted by complex 4 on Leishmania amazonensis promastigotes as well as it was
evidenced its potential against intramacrophage amastigotes. Complex 4 promoted a progressive reduction on
the promastigotes size and a remarkable increase on the granularity/complexity as judged by flow cytometry.
Transmission electron microscopy (TEM) analysis revealed extensive mitochondrial and plasma membrane alterations,
although plasma membrane integrity remained. The mitochondrial changes observed by TEM were
accompanied by a decrease in the activity of mitochondrial dehydrogenases with increased production of
reactive oxygen species. Interestingly, promastigotes also showed changes in lipid metabolism. Besides the very
low toxicity to macrophages, complex 4 had a great effect on intramacrophage amastigotes, displaying an IC50 of
3.91 μM. Collectively, the data presented here reinforce the potential of aminopyridyl compounds complexed to
zinc against L. amazonensis. Thus, our work serves as a basis for in vivo assays to be designed or even the synthesis
of more selective/effective compounds with lower cost. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Microbiologia Geral. Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Microbiologia Geral. Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Microbiologia Geral. Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Department of Chemistry, Maynooth University, Maynooth, Co. Kildare, Ireland. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Microbiologia Geral. Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | Leishmania amazonensis | pt_BR |
| Subject | Aminopyridyl | pt_BR |
| Subject | Metal chelator | pt_BR |
| Subject | Zinc complex | pt_BR |
| Subject | Anti-Leishmania action | pt_BR |
| Embargo date | 2023 | |
