Table of Contents
Journal of Amino Acids
Volume 2013, Article ID 178381, 12 pages
http://dx.doi.org/10.1155/2013/178381
Research Article

Amino Acid Derivatives as New Zinc Binding Groups for the Design of Selective Matrix Metalloproteinase Inhibitors

1Dipartimento di Chimica Farmaceutica e Tossicologica, Università di Napoli “Federico II,” Via D. Montesano 49, 80131 Napoli, Italy
2Dipartimento di Farmacia, Università degli Studi di Bari “Aldo Moro,” Via Orabona 4, 70125 Bari, Italy
3Dipartimento di Farmacia, Università degli Studi “G. d’Annunzio,” Via dei Vestini 31, 66013 Chieti, Italy
4Dipartimento di Scienze Farmaceutiche, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy
5Dipartimento di Scienze Farmaceutiche e Biomediche, Università degli Studi di Salerno, Via Ponte don Melillo, 84084 Fisciano, Italy

Received 21 December 2012; Accepted 28 January 2013

Academic Editor: Giuseppe De Rosa

Copyright © 2013 Mariateresa Giustiniano et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

A number of matrix metalloproteinases (MMPs) are important medicinal targets for conditions ranging from rheumatoid arthritis to cardiomyopathy, periodontal disease, liver cirrhosis, multiple sclerosis, and cancer invasion and metastasis, where they showed to have a dual role, inhibiting or promoting important processes involved in the pathology. MMPs contain a zinc (II) ion in the protein active site. Small-molecule inhibitors of these metalloproteins are designed to bind directly to the active site metal ions. In an effort to devise new approaches to selective inhibitors, in this paper, we describe the synthesis and preliminary biological evaluation of amino acid derivatives as new zinc binding groups (ZBGs). The incorporation of selected metal-binding functions in more complex biphenyl sulfonamide moieties allowed the identification of one compound able to interact selectively with different MMP enzymatic isoforms.