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.
- Applied Animal Behaviour Science - APPL ANIM BEHAV SCI. 01/1988; 20:259-273.
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ABSTRACT: The appropriate dose and the ability of exogenous ACTH to mimic the physiological effects of a real stressor need to be determined. In Exp. 1, 25 pregnant Brahman heifers were injected i.v. with either 0 (saline), .125, .25, .5, or 1 i.u. of ACTH/kg BW. Plasma cortisol was determined in blood samples collected during a 5-h period, and an integrated cortisol response was calculated for each cow. The greater the dose of ACTH, the greater was the integrated cortisol response (P < .001). However, peak plasma cortisol in response to the four doses of ACTH did not differ (P > .6). The plasma cortisol concentrations returned to baseline more slowly in those cows receiving the greater doses of ACTH, making their integrated areas of response greater. In Exp. 2, pregnant Brahman cows were either transported 48 km (n = 28), injected with 1 i.u. of ACTH/kg BW (n = 21), or served as shams (n = 28). Each treatment was repeated at 60, 80, 100, 120, and 140 d of gestation. Shrink was greater for the transported cows than for either the ACTH-treated or sham cows, 14.3, 6.0, and 5.2 kg (P < .001). Shrink also decreased in response to each subsequent application of treatment for all three treatment groups (P < .001). Transported cows had lower plasma cortisol concentrations after the first two applications of treatments (P < .006). The range of doses of ACTH caused a similar peak cortisol release; however, it took cortisol longer to return to baseline as ACTH dose increased. Repeated administration of exogenous ACTH did not cause the same amount of shrinkage as transportation, and the resultant cortisol concentrations remained consistent for each administration. There was no apparent carryover effect of repeated administration of ACTH at 20-d intervals. Maximal plasma cortisol concentrations in Brahman cattle can be obtained with doses of ACTH much smaller than those traditionally injected. However, larger doses of ACTH maintained plasma cortisol concentrations for a longer duration. Repeated transportation caused a decrease in cortisol release and shrinkage indicative of psychological habituation. Injections of ACTH did not cause the same physiological response as transportation.Journal of Animal Science 09/1996; 74(8):1806-11. · 2.09 Impact Factor
- Appl. Anim. Behav. Sci. 24 (1989) 157-167. 01/1989;