Pharmacokinetics, Metabolism, and in Vivo Efficacy of the Antimalarial Natural Product Bromophycolide A

A suite of pharmacokinetic and pharmacological studies show that bromophycolide A ( 1 ), an inhibitor of drug-sensitive and drug-resistant Plasmodium falciparum, displays a typical small molecule profile with low toxicity and good bioavailability. Despite susceptibility to liver metabolism and a short in vivo half-life, 1 significantly decreased parasitemia in a malaria mouse model. Combining these data with prior structure–activity relationship analyses, we demonstrate the potential for future development of 1 and its bioactive ester analogues.