TY - JOUR
T1 - Peptidomimetic inhibitors of farnesyltransferase with high in vitro activity and significant cellular potency
AU - Bolchi, Cristiano
AU - Pallavicini, Marco
AU - Rusconi, Chiara
AU - Diomede, Luisa
AU - Ferri, Nicola
AU - Corsini, Alberto
AU - Fumagalli, Laura
AU - Pedretti, Alessandro
AU - Vistoli, Giulio
AU - Valoti, Ermanno
PY - 2007/11/15
Y1 - 2007/11/15
N2 - 2-o-Tolyl or 2-o-anisyl substituted 4-hydroxy- and 4-carboxybenzamides of methionine, etherified and amidified with 2-hydroxymethyl- and 2-aminomethylpyridodioxane, respectively, are described as inhibitors of Ras protein farnesyltransferase (FTase). Of the sixteen compounds, resulting from the substitution pattern of benzamide and the configuration of the two stereocenters, seven inhibited FTase activity with potencies in the nanomolar range. They were all 2-oxymethylpyridodioxane ethers and, among them, the four o-tolyl substituted stereoisomers also showed micromolar antiproliferative effect on human aortic smooth muscle cells interfering with Ras farnesylation. The docking analysis enlightened significant differences in enzyme interaction between oxymethylpyridodioxane and aminomethylpyridodioxane derivatives.
AB - 2-o-Tolyl or 2-o-anisyl substituted 4-hydroxy- and 4-carboxybenzamides of methionine, etherified and amidified with 2-hydroxymethyl- and 2-aminomethylpyridodioxane, respectively, are described as inhibitors of Ras protein farnesyltransferase (FTase). Of the sixteen compounds, resulting from the substitution pattern of benzamide and the configuration of the two stereocenters, seven inhibited FTase activity with potencies in the nanomolar range. They were all 2-oxymethylpyridodioxane ethers and, among them, the four o-tolyl substituted stereoisomers also showed micromolar antiproliferative effect on human aortic smooth muscle cells interfering with Ras farnesylation. The docking analysis enlightened significant differences in enzyme interaction between oxymethylpyridodioxane and aminomethylpyridodioxane derivatives.
KW - Antiproliferative agents
KW - Antitumors
KW - Farnesyltransferase
KW - Peptidomimetic inhibitors
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U2 - 10.1016/j.bmcl.2007.09.015
DO - 10.1016/j.bmcl.2007.09.015
M3 - Article
C2 - 17889533
AN - SCOPUS:35148896320
VL - 17
SP - 6192
EP - 6196
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 22
ER -