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

A series of novel hybrids of CQ and astemizole have been shown to possess potent in vitro and in vivo antiplasmodial activity. 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.