Objective

To test the inhibitory activity of Ugi products 148B and 150D against Plasmodium Falciparum. For a summary of the project refer to this post.

Contributors

Jiri Gut from the Rosenthal group performed these experiments.

Procedure

The compounds are dissolved in DMSO as 10 mM stock then diluted 1:1000 into culture medium pH 7.4 (50 mM phosphate, 25 mM HEPES and bicarbonate buffers with 10% human serum). The parasites are then added and incubated for 48 hrs. Parasite development is measured by flow cytometry.

Results

compound
Test 1 IC-50 (nM)
SD
Test 2 IC-50 (nM)
SD
148B
7994
733
14335
120
150D
5411
241
8711
549
chloroquine
57.627
1.2
42
3

Discussion



Both Ugi products did inhibit Plasmodium Falciparum at concentrations 100-300 times that of chloroquine.
The food vacuole abnormality, which is indicative of cysteine protease inhibition was not observed in the parasites, suggesting other mode of action.

Conclusion

Both Ugi products proved to be inhibitors of Plasmodium Falciparum with IC-50s in the range of 5.4-14.3 micromolar.

Log

Tags



Phenanthrene-9-carboxaldehydeInChI=1/C15H10O/c16-10-12-9-11-5-1-2-6-13(11)15-8-4-3-7-14(12)15/h1-10H InChIKey: QECIGCMPORCORE-UHFFFAOYAE
tert-butylisocyanideInChI=1/C5H9N/c1-5(2,3)6-4/h1-3H3 InChIKey: FAGLEPBREOXSAC-UHFFFAOYAL
Crotonic Acid: InChI=1/C4H6O2/c1-2-3-4(5)6/h2-3H,1H3,(H,5,6)/f/h5H InChIKey: LDHQCZJRKDOVOX-UHFFFAOYAC
n-Heptylamine : InChI=1/C7H17N/c1-2-3-4-5-6-7-8/h2-8H2,1H3 InChIKey: WJYIASZWHGOTOU-UHFFFAOYAD
targetUgiExp148:InChI=1/C31H40N2O2/c1-6-8-9-10-15-21-33(28(34)16-7-2)29(30(35)32-31(3,4)5)
27-22-23-17-11-12-18-24(23)25-19-13-14-20-26(25)27/h7,11-14,16-20,22,29H,6,8-10,15,21H2,1-5H3,(H,32,35)/b16-7

Phenanthrene-9-carboxaldehydeInChI=1/C15H10O/c16-10-12-9-11-5-1-2-6-13(11)15-8-4-3-7-14(12)15/h1-10H InChIKey: QECIGCMPORCORE-UHFFFAOYAE
tert-butylisocyanideInChI=1/C5H9N/c1-5(2,3)6-4/h1-3H3 InChIKey: FAGLEPBREOXSAC-UHFFFAOYAL
Crotonic Acid: InChI=1/C4H6O2/c1-2-3-4(5)6/h2-3H,1H3,(H,5,6)/f/h5H InChIKey: LDHQCZJRKDOVOX-UHFFFAOYAC
benzylamine InChI=1/C7H9N/c8-6-7-4-2-1-3-5-7/h1-5H,6,8H2 InChIKey: WGQKYBSKWIADBV-UHFFFAOYAL
Ugi Product Exp150