Abstract

A number of matrix metalloproteinases (MMPs), proteins important in the balance of bone remodeling, play a critical role both in cancer metastasis and in bone matrix turnover associated with the presence of cancer cells in bone. Here, we report the synthesis and biological evaluation of a new class of MMP inhibitors characterized by a bisphosphonate function as the zinc binding group. Since the bisphosphonate group is also implicated in osteoclast inhibition and provides a preferential affinity to biological apatite, the new molecules can be regarded as bone-seeking medicinal agents. Docking experiments were performed to clarify the mode of binding of bisphosphonate inhibitors in the active site of MMP-2. The most promising of the studied bisphosphonates showed nanomolar inhibition against MMP-2 and resulted in potent inhibition of osteoclastic bone resorption in vitro.

Autore Pugliese

• Laghezza Antonio , Loiodice Fulvio , Tortorella Paolo

Tutti gli autori

• LAGHEZZA A.;LOIODICE F.;TORTORELLA P.

Titolo volume/Rivista

Non Disponibile

Anno di pubblicazione

2011

ISSN

1860-7179

ISBN

Non Disponibile

Numero di citazioni Wos

31

Ultimo Aggiornamento Citazioni

Non Disponibile

Numero di citazioni Scopus

32

Ultimo Aggiornamento Citazioni

Non Disponibile

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile