Straightforward synthesis of novel Akt inhibitors based on a glucose scaffold.
Glucose-based analogues of phosphatidylinositol 3-phosphate were straightforwardly synthesised from 2,3,4,6-tetra-O-acetyl-d-glucosyl bromide as protein kinase B (PKB/Akt) inhibitors. beta-d-Glucuronyl diethyl phosphoramidate was identified as a promising hit through biological screening in two different cellular systems. In addition, RNA interference experiments (siRNA) provide evidence of the ability of the compound to exert biological effects specifically through Akt signalling.
Cipolla
Laura
L
Department of Biotechnology and Biosciences, University of Milano-Bicocca P.za della Scienza 2, 20126 Milano, Italy. laura.cipolla@unimib.it
Redaelli
Cristina
C
Granucci
Francesca
F
Zampella
Giuseppe
G
Zaza
Antonio
A
Chisci
Riccardo
R
Nicotra
Francesco
F
D000818:Animals; D005947:Glucose / Q000737:chemistry*; D007294:Inositol / Q000737:chemistry; D008958:Models, Molecular; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D010716:Phosphatidylinositols / Q000737:chemistry; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000172:deficiency / Q000235:genetics; D034622:RNA Interference; D051381:Rats
D010716:Phosphatidylinositols; D047428:Protein Kinase Inhibitors; D007294:Inositol; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose