Author/Authors :
Armando Rossello، نويسنده , , Elisa Nuti، نويسنده , , Paolo Carelli، نويسنده , , Elisabetta Orlandini، نويسنده , , Marco Macchia، نويسنده , , Susanna Nencetti، نويسنده , , Maurizio Zandomeneghi، نويسنده , , Federica Balzano، نويسنده , , Gloria Uccello Barretta، نويسنده , , Adriana Albini، نويسنده , , Roberto Benelli، نويسنده , , Giovanni Cercignani، نويسنده , , Gillian Murphy، نويسنده , , Aldo Balsamo، نويسنده ,
Abstract :
Structural manipulation of the pharmacophoric model of type A selective MMP inhibitors (MMPi), obtained by the insertion of some alkyl substituents R2 possessing an appropriate geometry, steric bulkiness and lipophilicity, is able to improve potency, in the subnanomolar range on MMP-2, and to give a good MMP inhibition on MMP-14 (MT1-MMP) in the designed MMPi of type C, while maintaining a good MMP-1/MMP-2 selectivity profile. The simultaneous inhibition of these two enzymes yields type C compounds, which are potent antiangiogenic agents, able to block a chemoinvasion model on HUVEC cells in the micromolar range.
