Open AccessPharmacokinetics, Metabolism, and in Vivo Efficacy of the Antimalarial Natural Product Bromophycolide A
Author(s) -
Margaret E. Teasdale,
Jacques Prudhomme,
Manuel R. Torres,
Matthew Braley,
Serena Cervantes,
Shanti C. Bhatia,
James J. La Clair,
Karine Le Roch,
Julia Kubanek
Publication year - 2013
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/ml4002858
Subject(s) - pharmacokinetics , in vivo , pharmacology , plasmodium falciparum , natural product , bioavailability , malaria , parasitemia , drug metabolism , drug , metabolism , chemistry , biology , biochemistry , immunology , microbiology and biotechnology
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 SAR analyses, we demonstrate the potential for future development of 1 and its bioactive ester analogs.