| Texto completo | |
| Autor(es): Mostrar menos - |
do Espirito Santo, Rafael Dias
;
Arenas Velasquez, Angela Maria
;
Gushiken Passianoto, Luana Vitorino
;
Lopera Sepulveda, Alex Arbey
;
Clementino, Leandro da Costa
;
Assis, Renata Pires
;
Baviera, Amanda Martins
;
Kalaba, Predrag
;
dos Santos, Fabio Neves
;
Eberlin, Marcos Nogueira
;
Jose da Silva, Gil Valdo
;
Zehl, Martin
;
Lubec, Gert
;
Silva Graminha, Marcia Aparecida
;
Perez Gonzalez, Eduardo Rene
Número total de Autores: 15
|
| Tipo de documento: | Artigo Científico |
| Fonte: | EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY; v. 171, p. 13-pg., 2019-06-01. |
| Resumo | |
Leishmaniasis is a group of diseases caused by protozoan parasites from the genus Leishmania. There are estimated 1.3 million new cases annually with a mortality of 20,000-30,000 per year, when patients are left untreated. Current chemotherapeutic drugs available present high toxicity and low efficacy, the latter mainly due to the emergence of drug-resistant parasites, which makes discovery of novel, safe, and efficacious antileishmanial drugs mandatory. The present work reports the synthesis, characterization by ESI-MS, H-1 and C-13 NMR, and FTIR techniques as well as in vitro and in vivo evaluation of leishmanicidal activity of guanidines derivatives presenting lower toxicity. Among ten investigated compounds, all being guanidines containing a benzoyl, a benzyl, and a substituted phenyl moiety, LQOF-G2 (IC50-ama 5.6 mu M: SI = 131.8) and LQOF-G7 (IC50-ama 7.1 mu M; SI = 87.1) were the most active against L. amazonensis intracellular amastigote, showing low cytotoxicity to the host cells according to their selectivity index. The most promising compound, LQOF-G2, was further evaluated in an in vivo model and was able to decrease 60% of the parasite load in foot lesions at a dose of 0.25 mg/kg/day. Moreover, this guanidine derivative demonstrated reduced hepatotoxicity compared to other leishmanicidal compounds and did not show nephrotoxicity, as determined by the analyses of biomarkers of hepatic damage and renal function, which make this compound a potential new hit for therapy against leishmaniasis. (C) 2019 Elsevier Masson SAS. All rights reserved. (AU) | |
| Processo FAPESP: | 13/24487-6 - Estudo de reações de síntese limpa e modificação química do biodiesel e óleo fúsel para preparação de carbonatos e carbamatos orgânicos utilizando dióxido de carbono na presença de organocatalisadores e catalisadores heterogêneos |
| Beneficiário: | Eduardo Rene Perez Gonzalez |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 17/03552-5 - Leishmanioses: do screening ao estudo de mecanismos de ação, uma contribuição para a descoberta de novas moléculas bioativas |
| Beneficiário: | Marcia Aparecida Silva Graminha |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 13/08248-1 - Leishmanioses e compostos bioinorgânicos de ouro(I) e paládio(II): atividade leishmanicida, mecanismos de ação e potenciais novos alvos terapêuticos |
| Beneficiário: | Marcia Aparecida Silva Graminha |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 16/19289-9 - Caracterização do mecanismo de morte celular potencialmente induzida pelo antileishmanial binuclear ciclopaladado CP2: uma contribuição para o desenvolvimento racional de fármacos |
| Beneficiário: | Angela Maria Arenas Velásquez |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |