4(1H)-quinolones with liver stage activity against Plasmodium berghei

Alexis N. LaCrue, Fabián E. Sáenz, R. Matthew Cross, Kenneth O. Udenze, Andrii Monastyrskyi, Steven Stein, Tina S. Mutka, Roman Manetsch, Dennis E. Kyle

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

26 Citas (Scopus)

Resumen

With the exception of primaquine, tafenoquine, and atovaquone, there are very few antimalarials that target liver stage parasites. In this study, a transgenic Plasmodium berghei parasite (1052Cl1; PbGFP-Luccon) that expresses luciferase was used to assess the anti-liver stage parasite activity of ICI 56,780, a 7-(2-phenoxyethoxy)-4(1H)-quinolone (PEQ), as well as two 3-phenyl-4(1H)-quinolones (P4Q), P4Q-146 and P4Q-158, by using bioluminescent imaging (BLI). Results showed that all of the compounds were active against liver stage parasites; however, ICI 56,780 and P4Q-158 were the most active, with low nanomolar activity in vitro and causal prophylactic activity in vivo. This potent activity makes these compounds ideal candidates for advancement as novel antimalarials.

Idioma originalInglés
Páginas (desde-hasta)417-424
Número de páginas8
PublicaciónAntimicrobial Agents and Chemotherapy
Volumen57
N.º1
DOI
EstadoPublicada - ene. 2013

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