N10,N11-di-alkylamine indolo[3,2-b]quinolines as hemozoin inhibitors: design, synthesis and antiplasmodial activity.
Bioorg Med Chem
; 23(7): 1530-9, 2015 Apr 01.
Article
en En
| MEDLINE
| ID: mdl-25725608
ABSTRACT
We recently reported that potent N10,O11-bis-alkylamine indolo[3,2-b]quinoline antimalarials act as hemozoin (Hz) growth inhibitors. To improve access and binding to the target we have now designed novel N10,N11-di-alkylamine bioisosteres. 3-Chloro derivatives (10a-f) showed selectivity for malaria parasite compared to human cells, high activity against Plasmodium falciparum chloroquine (CQ)-resistant strain W2 (IC50s between 20 and 158nM), good correlation with ß-hematin inhibition and improved vacuolar accumulation ratios, thus suggesting inhibition of Hz growth as one possible mechanism of action for these compounds. Moreover, our studies show that Hz is a valid target for the development of new antimalarials able to overcome CQ resistance.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Plasmodium falciparum
/
Quinolinas
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Diseño de Fármacos
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Hemoproteínas
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Antimaláricos
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Portugal