| Author | Vasconcelos, Mariela Ferreira de | |
| Author | Cunha Júnior, Edézio Ferreira da | |
| Author | Andrade Neto, Valter Viana de | |
| Author | Siqueira, Larissa Moreira | |
| Author | Levy, Claudia Masini d'Avila | |
| Author | Moreth, Marcele | |
| Author | Cunico, Wilson | |
| Author | Souza, Marcus Vinicius Nora de | |
| Author | Gomes, Cláudia Regina Brandão | |
| Author | Santos, Eduardo Caio Torres | |
| Access date | 2015-05-04T16:34:36Z | |
| Available date | 2015-05-04T16:34:36Z | |
| Document date | 2014 | |
| Citation | VASCONCELOS, Mariela Ferreira de et al. Oral effectiveness of PMIC4, a novel hydroxyethylpiperazine analogue, in Leishmania amazonensis. International Journal for Parasitology: Drugs and Drug Resistance, v.4, n,3, p.210-213, 2014. | pt_BR |
| ISSN | 2211-3207 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/10184 | |
| Language | eng | pt_BR |
| Publisher | ScienceDirect | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Leishmania | pt_BR |
| Title | Oral effectiveness of PMIC4, a novel hydroxyethylpiperazine analogue, in Leishmania amazonensis | pt_BR |
| Type | Article | |
| DOI | 10.1016/j.ijpddr.2014.10.005 | pt_BR |
| Abstract | Pentavalent antimonials have saved the lives of thousands of Leishmania-infected patients more than seventy
years but, unfortunately, they are highly toxic and require parenteral delivery. Therefore, the search
for safer and orally delivered alternative is a need. This paper describes the antileishmanial properties of
PMIC4, a novel hydroxyethylpiperazine analogue. PMIC4 showed potent activity against intracellular
amastigotes of Leishmania amazonensis, with IC50 of 1.8 lM and selectivity index higher than 100-fold,
calculated in relation to the toxicity on the host cell. Following laboratory animal welfare policies, we
analyzed the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties and calculated
the Lipinski’s rule of five of PMIC4 before proceeding to in vivo tests. PMIC4 satisfied Lipinski’s rule
of five and presented high probability of human intestinal absorption, suggesting a good chance of druglikeness
and oral bioavailability. For in vivo studies, PMIC4 was administered via intralesional injection
(3.4 mg/kg/day, three times a week) or orally (34.0 mg/kg/day, five times a week) to L. amazonensisinfected
BALB/c mice throughout the 98 day experiments. At the end of the treatment period, serum
markers of toxicity were measured. When administered orally, PMIC4 controlled the lesions in L. amazonensis-
infected BALB/c mice without altering serological markers of toxicity. These results demonstrate
that PMIC4 is a promising molecular scaffold, orally effective against experimental leishmaniasis. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Farmanguinhos. Departamento de Síntese de Fármacos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal de Pelotas. Centro de Ciências Químicas, Farmacêuticas e de Alimentos. Laboratório de Química Aplicada à Bioativos. Pelotas, RS, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Farmanguinhos. Departamento de Síntese de Fármacos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Farmanguinhos. Departamento de Síntese de Fármacos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanosomatídeos. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | Leishmaniasis chemotherapy | pt_BR |
| Subject | Hydroxyethylamines | pt_BR |
| Subject | Oral bioavailability | pt_BR |
| Subject | In silico ADMET | pt_BR |
| Subject in Spanish | Leishmania | pt_BR |
| DeCS | Ciências Biológicas | pt_BR |
