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Design, synthesis and biological evaluation of sugar-derived Ras inhibitors |
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| Authors: | Peri Francesco Airoldi Cristina Colombo Sonia Martegani Enzo van Neuren Anske Stephanie Stein Matthias Marinzi Chiara Nicotra Francesco |
| Affiliation: | Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy. francesco.peri@unimib.it |
| Abstract: | The design and synthesis of novel Ras inhibitors with a bicyclic scaffold derived from the natural sugar D-arabinose are presented. Molecular modelling showed that these ligands can bind Ras by accommodating the aromatic moieties and the phenylhydroxylamino group in a cavity near the Switch II region of the protein. All the synthetic compounds were active in inhibiting nucleotide exchange on p21 human Ras in vitro, and two of them selectively inhibited Ras-dependent cell growth in vivo. |
| Keywords: | ab initio calculations antitumor agents drug design inhibitors medicinal chemistry |
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