当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Potent naphthoquinones against antimony-sensitive and -resistant Leishmania parasites: synthesis of novel α- and nor-α-lapachone-based 1,2,3-triazoles by copper-catalyzed azide-alkyne cycloaddition.

Potent naphthoquinones against antimony-sensitive and -resistant Leishmania parasites: synthesis of novel α- and nor-α-lapachone-based 1,2,3-triazoles by copper-catalyzed azide-alkyne cycloaddition.

Abstract：

:Continuing our screening program for novel anti-parasite compounds, we synthesized seven 1,4-naphthoquinones coupled to 1,2,3-triazoles, five nor-β-lapachone-based 1,2,3-triazoles and ten α-lapachone-based 1,2,3-triazoles. These and other naphthoquinonoid compounds were evaluated for their activity against promastigote forms of antimony-sensitive and -resistant strains of Leishmania infantum (syn. Leishmania chagasi) and Leishmania amazonensis. The toxicity of these compounds to mammalian cells was also examined. The substances were more potent than an antimonial drug, with IC50 values ranging from 1.0 to 50.7 μM. Nor-α-lapachone derivatives showed the highest antileishmanial activity, with selectivity indices in the range of 10-15. These compounds emerged as important leads for further investigation as antileishmanial agents. Additionally, one of these compounds exhibited cross-resistance in Sb-resistant Leishmania and could provide a molecular tool for investigating the multidrug resistance mechanisms in Leishmania parasites.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Guimarães TT,Pinto Mdo C,Lanza JS,Melo MN,do Monte-Neto RL,de Melo IM,Diogo EB,Ferreira VF,Camara CA,Valença WO,de Oliveira RN,Frézard F,da Silva EN Jr

doi

10.1016/j.ejmech.2013.02.038

subject

Has Abstract

pub_date

2013-05-01 00:00:00

pages

523-30

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(13)00145-1

journal_volume

63

pub_type

杂志文章

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