Table of Contents
Journal of Amino Acids
Volume 2013, Article ID 606282, 7 pages
Research Article

Design, Synthesis, and Evaluation of New Tripeptides as COX-2 Inhibitors

1Dipartimento di Scienze Farmaceutiche e Biomediche, Università degli Studi di Salerno, Via Ponte don Melillo, 84084 Fisciano, Italy
2Dipartimento di Chimica Farmaceutica e Tossicologica, Università degli Studi di Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy
3Dipartimento Farmaco-Biologico, Università degli Studi di Messina, Viale Annunziata, 98168 Messina, Italy
4Dipartimento di Biochimica e Biofisica, Seconda Università degli Studi di Napoli, Via L. De Crecchio 7, 80138 Napoli, Italy
5Dipartimento di Scienze della Salute, Università degli Studi “Magna Græcia” di Catanzaro, Campus Universitario “S. Venuta”, Viale Europa, 88100 Catanzaro, Italy

Received 21 December 2012; Accepted 17 January 2013

Academic Editor: Michele Caraglia

Copyright © 2013 Ermelinda Vernieri 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.


Cyclooxygenase (COX) is a key enzyme in the biosynthetic pathway leading to the formation of prostaglandins, which are mediators of inflammation. It exists mainly in two isoforms COX-1 and COX-2. The conventional nonsteroidal anti-inflammatory drugs (NSAIDs) have gastrointestinal side effects because they inhibit both isoforms. Recent data demonstrate that the overexpression of these enzymes, and in particular of cyclooxygenases-2, promotes multiple events involved in tumorigenesis; in addition, numerous studies show that the inhibition of cyclooxygenases-2 can delay or prevent certain forms of cancer. Agents that inhibit COX-2 while sparing COX-1 represent a new attractive therapeutic development and offer a new perspective for a further use of COX-2 inhibitors. The present study extends the evaluation of the COX activity to all 203 possible natural tripeptide sequences following a rational approach consisting in molecular modeling, synthesis, and biological tests. Based on data obtained from virtual screening, only those peptides with better profile of affinity have been selected and classified into two groups called S and E. Our results suggest that these novel compounds may have potential as structural templates for the design and subsequent development of the new selective COX-2 inhibitors drugs.