title: The antiplasmodial activity of norcantharidin analogs.
abstract: The antiplasmodial activities of sixty norcantharidin analogs were tested in vitro against a chloroquine sensitive (D6, Sierra Leone) and chloroquine resistant (W2) strains of Plasmodium falciparum. Forty analogs returned IC(50) values <500 μM against at least one of the P. falciparum strains examined. The ring open compound 24 ((1S,4R)-3-(allylcarbamoyl)-7-oxabicyclo[2.2.1]heptane-2-carboxylic acid) is the most active aliphatic analog (D6 IC(50)=3.0±0.0 and W2 IC(50)=3.0±0.8 μM) with a 20-fold enhancement relative to norcantharidin. Surprisingly, seven norcantharimides also displayed good antiplasmodial activity with the most potent, 5 returning D6=8.9±0.9 and W2 IC(50)=12.5±2.2 μM, representing a fivefold enhancement over norcantharidin.
authors.affiliation: USDA, ARS, Natural Products Utilization Research Unit, University, MS 38677, USA. jbajsa@olemiss.edu
authors.forename: Joanna
authors.initials: J
authors.lastname: Bajsa
authors.forename: Adam
authors.initials: A
authors.lastname: McCluskey
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Gordon
authors.forename: Scott G
authors.initials: SG
authors.lastname: Stewart
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Hill
authors.forename: Rajnish
authors.initials: R
authors.lastname: Sahu
authors.forename: Stephen O
authors.initials: SO
authors.lastname: Duke
authors.forename: Babu L
authors.initials: BL
authors.lastname: Tekwani
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D006801:Humans; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000187:drug effects*; D017386:Sequence Homology, Amino Acid
chemical_list: D000962:Antimalarials; D019086:Bridged Bicyclo Compounds, Heterocyclic; C069741:norcantharidin