Targeting the Cytochrome bc1 Complex of Leishmania Parasites for Discovery of Novel Drugs.
Antimicrob Agents Chemother
; 60(8): 4972-82, 2016 08.
Article
em En
| MEDLINE
| ID: mdl-27297476
ABSTRACT
Endochin-like quinolones (ELQs) are potent and specific inhibitors of cytochrome bc1 from Plasmodium falciparum and Toxoplasma gondii and show promise for novel antiparasitic drug development. To determine whether the mitochondrial electron transport chain of Leishmania parasites could be targeted similarly for drug development, we investigated the activity of 134 structurally diverse ELQs. A cohort of ELQs was selectively toxic to amastigotes of Leishmania mexicana and L. donovani, with 50% inhibitory concentrations (IC50s) in the low micromolar range, but the structurally similar hydroxynaphthoquinone buparvaquone was by far the most potent inhibitor of electron transport, ATP production, and intracellular amastigote growth. Cytochrome bc1 is thus a promising target for novel antileishmanial drugs, and further improvements on the buparvaquone scaffold are warranted for development of enhanced therapeutics.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Complexo III da Cadeia de Transporte de Elétrons
/
Quinolonas
/
Leishmania
/
Antiprotozoários
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article