The antiplasmodial activity of norcantharidin analogs.
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.
Bajsa
Joanna
J
USDA, ARS, Natural Products Utilization Research Unit, University, MS 38677, USA. jbajsa@olemiss.edu
McCluskey
Adam
A
Gordon
Christopher P
CP
Stewart
Scott G
SG
Hill
Timothy A
TA
Sahu
Rajnish
R
Duke
Stephen O
SO
Tekwani
Babu L
BL
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
D000962:Antimalarials; D019086:Bridged Bicyclo Compounds, Heterocyclic; C069741:norcantharidin