Quinoline-benzofuran and quinoline-benzothiophene derivatives as antiplasmodium agents

Two series of coupled heterocyclic systems have been synthesised and found to be efficacious against the NF54 chloroquine sensitive strain of P. falciparum in an in vitro assay. Quinolines were coupled with benzofurans in the first series and benzothiophenes in the second series. Compounds with an amide linkage are more efficacious by one order of magnitude than the ester equivalent. No other clear pattern was discernible. Compounds were also tested for toxicity using an MTT assay. All compounds tested showed selectivity towards P. falciparum. Barring one, all compounds tested showed greater efficacy than chloroquine against β-hematin inhibition. But no correlation was observed between β-hematin inhibition and efficacy against P. falciparum.