Synthesis and in vitro SAR evaluation of natural vanillin-based chalcones tethered quinolines as antiplasmodial agents

Abstract In pursuit of antimalarial drug, to overcome the drug resistance and the risk of drug-drug interactions, the chalcone hybrids and their structure-activity relationship for the antimalarial activity studied against chloroquine sensitive as well as multi-drug resistant strain of Plasmodium falciparum. Our study has revealed that 7- Chloro quinoline groups on chalcone increase anti-malarial potency, while the positional interchange of these groups decreases the efficacy. Particularly, chloro-substituent provided potent analogues which were easily derived from naturally available vanillin. The most active compounds were relatively non-toxic and structure-activity relationship study suggested that 7-chloroquinoline group when attached with triazole linkage increased the antimalarial potential of the compound against both chloroquine-sensitive and multidrug resistant strain.