Design, modelling, synthesis and biological evaluation of peptidomimetic phosphinates as inhibitors of matrix metalloproteinases MMP-2 and MMP-8

Gianluca Bianchini; Massimiliano Aschi; Giancarlo Cavicchio; Marcello Crucianelli; Serena Preziuso; Carlo Gallina; Adele Nastari; Enrico Gavuzzo; Fernando Mazza

doi:10.1016/j.bmc.2005.04.079

Design, modelling, synthesis and biological evaluation of peptidomimetic phosphinates as inhibitors of matrix metalloproteinases MMP-2 and MMP-8

Bioorg Med Chem. 2005 Aug 1;13(15):4740-9. doi: 10.1016/j.bmc.2005.04.079.

Authors

Gianluca Bianchini¹, Massimiliano Aschi, Giancarlo Cavicchio, Marcello Crucianelli, Serena Preziuso, Carlo Gallina, Adele Nastari, Enrico Gavuzzo, Fernando Mazza

Affiliation

¹ Dipartimento di Chimica, Ingegneria Chimica e Materiali, Università dell'Aquila, via Vetoio, I-67010-Coppito, AQ, Italy.

PMID: 15935680
DOI: 10.1016/j.bmc.2005.04.079

Abstract

Three novel peptidomimetic phosphinate inhibitors have been synthesized and evaluated as inhibitors of matrix metalloproteinases MMP-2 and MMP-8. Their IC50 values are in the micromolar range, and one of them showed to be the most effective inhibitor of MMP-2. The differences in binding affinities for MMP-2 and MMP-8 of the three phosphinates have been rationalized by means of modelling studies and molecular dynamics simulations.

Publication types

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

MeSH terms

Drug Design*
Inhibitory Concentration 50
Matrix Metalloproteinase 2 / metabolism
Matrix Metalloproteinase 8 / metabolism
Matrix Metalloproteinase Inhibitors*
Models, Chemical*
Molecular Structure
Phosphorous Acids / chemical synthesis
Phosphorous Acids / chemistry*
Phosphorous Acids / pharmacology
Protease Inhibitors / chemical synthesis*
Protease Inhibitors / chemistry
Protease Inhibitors / pharmacology*

Substances

Matrix Metalloproteinase Inhibitors
Phosphorous Acids
Protease Inhibitors
Matrix Metalloproteinase 2
Matrix Metalloproteinase 8
metaphosphoric acid