Straightforward synthesis of novel Akt inhibitors based on a glucose scaffold

Laura Cipolla; Cristina Redaelli; Francesca Granucci; Giuseppe Zampella; Antonio Zaza; Riccardo Chisci; Francesco Nicotra

doi:10.1016/j.carres.2009.12.013

Straightforward synthesis of novel Akt inhibitors based on a glucose scaffold

Carbohydr Res. 2010 Jul 2;345(10):1291-8. doi: 10.1016/j.carres.2009.12.013. Epub 2009 Dec 16.

Authors

Laura Cipolla¹, Cristina Redaelli, Francesca Granucci, Giuseppe Zampella, Antonio Zaza, Riccardo Chisci, Francesco Nicotra

Affiliation

¹ Department of Biotechnology and Biosciences, University of Milano-Bicocca P.za della Scienza 2, 20126 Milano, Italy. laura.cipolla@unimib.it

PMID: 20044079
DOI: 10.1016/j.carres.2009.12.013

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Glucose / chemistry*
Inositol / chemistry
Models, Molecular
Myocytes, Cardiac / drug effects
Myocytes, Cardiac / metabolism
Phosphatidylinositols / chemistry
Protein Kinase Inhibitors / chemical synthesis*
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology*
Protein Structure, Tertiary
Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
Proto-Oncogene Proteins c-akt / chemistry
Proto-Oncogene Proteins c-akt / deficiency
Proto-Oncogene Proteins c-akt / genetics
RNA Interference
Rats

Substances

Phosphatidylinositols
Protein Kinase Inhibitors
Inositol
Proto-Oncogene Proteins c-akt
Glucose