Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 49, Issue 11, Pages 3345-3353Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm0600545
Keywords
-
Categories
Ask authors/readers for more resources
After the discovery of a potent natural flavonoid glucoside as a potent inhibitor of FabI, a large flavonoid library was screened against three important enzymes (i.e., FabG, FabZ, and FabI) involved in the fatty acid biosynthesis of P. falciparum. Although flavones with a simple hydroxylation pattern (compounds 4-9) showed moderate inhibitory activity toward the enzymes tested (IC50 10-100 mu M), the more complex flavonoids (12-16) exhibited strong activity toward all three enzymes (IC50 0.5-8 mu M). Isoflavonoids 2628 showed moderate (IC50 7-30 mu M) but selective activity against FabZ. The most active compounds were C-3 gallic acid esters of catechins (32, 33, 37, 38), which are strong inhibitors of all three enzymes (IC50 0.2-1.1 mu M). Kinetic analysis using luteolin (12) and (-)-catechin gallate (37) as model compounds revealed that FabG was inhibited in a noncompetitive manner. FabZ was inhibited competitively, whereas both compounds behaved as tight-binding noncompetitive inhibitors of FabI. In addition, these polyphenols showed in vitro activity against chloroquine-sensitive (NF54) and -resistant (K1) P. falciparum strains in the low to submicromolar range.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available