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

Authors :
Vernieri, Ermelinda
Gomez-Monterrey, Isabel
Milite, Ciro
Grieco, Paolo
Musella, Simona
Bertamino, Alessia
Scognamiglio, Ilaria
Alcaro, Stefano
Artese, Anna
Ortuso, Francesco
Novellino, Ettore
Sala, Marina
Campiglia, Pietro
Source :
Journal of Amino Acids; 2013, Vol. 2013 Issue: 1
Publication Year :
2013

Abstract

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.

Details

Language :
English
ISSN :
20900104 and 20900112
Volume :
2013
Issue :
1
Database :
Supplemental Index
Journal :
Journal of Amino Acids
Publication Type :
Periodical
Accession number :
ejs37527830
Full Text :
https://doi.org/10.1155/2013/606282