Chloroquine-astemizole hybrids with potent in vitro and in vivo antiplasmodial activity

Chitalu C Musonda; Gavin A Whitlock; Michael J Witty; Reto Brun; Marcel Kaiser

doi:10.1016/j.bmcl.2008.11.047

Chloroquine-astemizole hybrids with potent in vitro and in vivo antiplasmodial activity

Bioorg Med Chem Lett. 2009 Jan 15;19(2):481-4. doi: 10.1016/j.bmcl.2008.11.047. Epub 2008 Nov 18.

Authors

Chitalu C Musonda¹, Gavin A Whitlock, Michael J Witty, Reto Brun, Marcel Kaiser

Affiliation

¹ Department of Chemistry, University of Cape Town, P/B Rondebosch 7700, Cape Town, South Africa.

PMID: 19054674
DOI: 10.1016/j.bmcl.2008.11.047

Abstract

A dual activity, conjugated approach has been taken to form hybrid molecules of two known antimalarial drugs, chloroquine (CQ) and the non-sedating H1 antagonist astemizole. A variety of linkers were investigated to conjugate the two agents into one molecule. Compounds 5-8 possessed improved in vitro activity against a CQ-resistant strain of Plasmodium falciparum, and examples 7 and 8 were active in vivo in mouse models of malaria.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antimalarials / chemistry*
Antimalarials / pharmacology*
Antimalarials / therapeutic use
Astemizole / chemistry*
Astemizole / pharmacology
Astemizole / therapeutic use
Chloroquine / chemistry*
Chloroquine / pharmacology
Chloroquine / therapeutic use
Disease Models, Animal
Drug Evaluation, Preclinical
Malaria, Falciparum / drug therapy
Mice
Plasmodium falciparum / drug effects*

Substances

Antimalarials
Astemizole
Chloroquine