Exp165

=Objective= To test the inhibitory activity of Ugi products 148B and 150D ([|Ugi product Exp150])against falcipain-2. 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 1:100 into 100 mM acetate buffer (pH 6.0) then pre-incubated with the falcipain-2 enzyme. Fluorogenic substrate is then added (Z-LEU-ARG-aminomethylcoumarin) and the signal read over time. The results are expressed as percent of control (DMSO), and IC 50 calculated. =Results= = = =Discussion=
 * **compound** || **Test 1 IC50(nM)** || **SD** || **Test 2 IC50(nM)** || **SD** ||
 * 148B || 5284 || 344 || 19655 || 1874 ||
 * 150D || 4718 || 448 || 16660 || 2319 ||
 * [|E64] || 105.55 || 2.3 || 64 || 2 ||

The 2 Ugi products exhibited similar activity. In the first test the compounds were about 50 times less active than the Rosenthal positive control E64. In the second test they were about 300 times less active than E64. It is unclear why the activities of both compounds decreased about fourfold in the second run. Compounds were stored as DMSO solutions at -20C. Degradation over time is one possibility but the fact that these are essentially insoluble in water may render the experiments less reproducible. Further studies in liposomal formulations should be performed to overcome the solubility problem. =Conclusion= Both Ugi products proved to be inhibitors of falcipain-2 with IC-50s in the range of 4.7-19.7 micromolar. =Log=

=Tags=

[|Phenanthrene-9-carboxaldehyde][|InChI=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-butylisocyanide][|InChI=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-carboxaldehyde][|InChI=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-butylisocyanide][|InChI=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]