1 research outputs found
Foxo3a Inhibitors of Microbial Origin, JBIR-141 and JBIR-142
JBIR-141 (<b>1</b>) and JBIR-142
(<b>2</b>) were discovered
as potent Foxo3a inhibitors that consist of three quite unique substructures,
a 1-((dimethylamino)Âethyl)-5-methyl-4,5-dihydrooxazole-4-carboxylic
acid that is originated from Ala-Thr amino acid residues, a 3-acetoxy-4-amino-7-(hydroxyÂ(nitroso)Âamino)-2,2-dimethylheptanoic
acid, and an α-acyl tetramic acid fused with a 2-methylpropan-1-ol
moiety. Their structures involving absolute configurations were determined
by spectroscopic data, chemical degradation, anisotropy methods, and
LC–MS analyses of diastereomeric derivatives. Compounds <b>1</b> and <b>2</b> exhibited specific inhibition against
Foxo3a transcriptional activity with IC<sub>50</sub> values of 23.1
and 166.2 nM, respectively