Exploration of potential prodrug approach of the bis-thiazolium salts T3 and T4 for orally delivered antimalarials.
Bioorg Med Chem Lett
; 20(13): 3953-6, 2010 Jul 01.
Article
en En
| MEDLINE
| ID: mdl-20605450
ABSTRACT
We report here the synthesis and biological evaluation of a series of 37 compounds as precursors of potent antimalarial bis-thiazolium salts (T3 and T4). These prodrugs were either thioester, thiocarbonate or thiocarbamate type and were synthesized in one step by reaction of an alkaline solution of the parent drug with the appropriate activated acyl group. Structural variations affecting physicochemical properties were made in order to improve oral activity. Twenty-five of them exhibited potent antimalarial activity with IC(50) lower than 7nM against Plasmodium falciparum in vitro. Notably, 3 and 22 showed IC(50)=2.2 and 1.8nM, respectively. After oral administration 22 was the most potent compound clearing the parasitemia in Plasmodium vinckei infected mice with a dose of 1.3mg/kg.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Plasmodium
/
Sales (Química)
/
Tiazoles
/
Profármacos
/
Malaria
/
Antimaláricos
Límite:
Animals
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Francia