1,1′-disubstituted ferrocenyl carbohydrate chloroquine conjugates as potential antimalarials

Christoph Herrmann, Paloma F. Salas, Jacqueline F. Cawthray, Carmen De Kock, Brian O. Patrick, Peter J. Smith, Michael J. Adam, Chris Orvig

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

34 Citas (Scopus)

Resumen

This work presents a new class of organometallic antimalarials, based on a ferrocene scaffold, bearing a chloroquine derivative and a 1,2;3,5- (diisopropylidene)-α-d-glucofuranose moiety in a 1,1′-heteroannular substitution pattern. Synthesis proceeds via orthogonal functionalization of ferrocene, giving 1-acetoxy-1′-(1,3-dioxan-2-yl)ferrocene (15) as the precursor for modular introduction of the carbohydrate (16, 17) followed by subsequent reductive amination with chloroquine building blocks 8-10, yielding the 1-[3-(7-chloroquinolin-4-ylamino)alkylamino]-1′-[6-(1,2;3,5- diisopropylidene)-α-d-glucofuranosidyl]ferrocenes 18-20. After complete characterization of these new, trifunctional conjugates, they were examined for their antiplasmodial activity in a chloroquine-susceptible strain of Plasmodium falciparum (D10) and in two chloroquine-resistant strains (Dd2 and K1). Their activity was compared to that of the monosubstituted reference conjugates 1-3 and the 1,2-disubstituted regioisomers 4-6. Compounds 19 and 20 exhibited consistently high activity in in vitro antiplasmodial activity assays performed in Dd2 and K1 strains, performing better than the reference compounds chloroquine and the monosubstituted and 1,2-disubstituted compounds 1-6.

Idioma originalInglés
Páginas (desde-hasta)5736-5747
Número de páginas12
PublicaciónOrganometallics
Volumen31
N.º16
DOI
EstadoPublicada - 27 ago. 2012
Publicado de forma externa

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Profundice en los temas de investigación de '1,1′-disubstituted ferrocenyl carbohydrate chloroquine conjugates as potential antimalarials'. En conjunto forman una huella única.

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