Synthesis and antimalarial activity of (E) 2-(2′-chloro-3′-quinolinyl-methylidene)-5,7-dimethoxyindanones

A series of (E) 2-quinolinylmethylidene-5,7-dimethoxyindanones were prepared via base catalyzed Claisen-Schmidt condensation of 5,7-dimethoxy-1-indanone with the appropriate 2-chloro-3-formylquinoline derivative. Evaluation of their in vitro inhibition of beta-hematin formation and hemoglobin hydrolysis and in vivo efficacy in rodent Plasmodium berghei suggest the antimalarial activity is derived from inhibition of hemoglobinolytic proteases.