Busca avançada
Ano de início
Entree
(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Potential of 2-Hydroxy-3-Phenylsulfanylmethyl-[1,4]-Naphthoquinones against Leishmania (L.) infantum: Biological Activity and Structure-Activity Relationships

Texto completo
Autor(es):
Pinto, Erika G. [1, 2] ; Santos, Isabela O. [3] ; Schmidt, Thomas J. [4] ; Borborema, Samanta E. T. [2] ; Ferreira, Vitor F. [3] ; Rocha, David R. [3] ; Tempone, Andre G. [2]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Med Trop Sao Paulo, Sao Paulo - Brazil
[2] Adolfo Lutz Inst, Ctr Parasitol & Mycol, Sao Paulo - Brazil
[3] Univ Fed Fluminense, Inst Quim, Dept Quim Organ, Niteroi, RJ - Brazil
[4] Univ Munster, Inst Pharmaceut Biol & Phytochem, D-48149 Munster - Germany
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: PLoS One; v. 9, n. 8 AUG 29 2014.
Citações Web of Science: 30
Resumo

Naphtoquinones have been used as promising scaffolds for drug design studies against protozoan parasites. Considering the highly toxic and limited therapeutic arsenal, the global negligence with tropical diseases and the elevated prevalence of co-morbidities especially in developing countries, the parasitic diseases caused by various Leishmania species (leishmaniasis) became a significant public health threat in 98 countries. The aim of this work was the evaluation of antileishmanial in vitro potential of thirty-six 2-hydroxy-3-phenylsulfanylmethyl-{[}1,4]-naphthoquinones obtained by a three component reaction of lawsone, the appropriate aldehyde and thiols adequately substituted, exploiting the in situ generation of o-quinonemethides (o-QM) via the Knoevenagel condensation. The antileishmanial activity of the naphthoquinone derivatives was evaluated against promastigotes and intracellular amastigotes of Leishmania (Leishmania) infantum and their cytotoxicity was verified in mammalian cells. Among the thirty-six compounds, twenty-seven were effective against promastigotes, with IC50 values ranging from 8 to 189 mu M; fourteen compounds eliminated the intracellular amastigotes, with IC50 values ranging from 12 to 65 mu M. The compounds containing the phenyl groups at R-1 and R-2 and with the fluorine substituent at the phenyl ring at R-2, rendered the most promising activity, demonstrating a selectivity index higher than 15 against amastigotes. A QSAR (quantitative structure activity relationship) analysis yielded insights into general structural requirements for activity of most compounds in the series. Considering the in vitro antileishmanial potential of 2-hydroxy-3-phenylsulfanylmethyl-{[}1,4]-naphthoquinones and their structure-activity relationships, novel lead candidates could be exploited in future drug design studies for leishmaniasis. (AU)

Processo FAPESP: 11/23703-1 - Estudo do potencial terapêutico de fármacos e compostos sintéticos, livres ou incluídos em nanolipossomos: uma abordagem in vitro e experimental
Beneficiário:Érika Gracielle Pinto
Linha de fomento: Bolsas no Brasil - Doutorado
Processo FAPESP: 12/18756-1 - Avaliação de novas alternativas terapêuticas com fármacos sintéticos em modelos in vitro e experimentais de Leishmania (L.) infantum chagasi
Beneficiário:André Gustavo Tempone Cardoso
Linha de fomento: Auxílio à Pesquisa - Regular