title: Design, Synthesis, and Evaluation of New Tripeptides as COX-2 Inhibitors.
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 20(3) 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.
authors.affiliation: Dipartimento di Scienze Farmaceutiche e Biomediche, Università degli Studi di Salerno, Via Ponte don Melillo, 84084 Fisciano, Italy.
authors.forename: Ermelinda
authors.initials: E
authors.lastname: Vernieri
authors.forename: Isabel
authors.initials: I
authors.lastname: Gomez-Monterrey
authors.forename: Ciro
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authors.lastname: Milite
authors.forename: Paolo
authors.initials: P
authors.lastname: Grieco
authors.forename: Simona
authors.initials: S
authors.lastname: Musella
authors.forename: Alessia
authors.initials: A
authors.lastname: Bertamino
authors.forename: Ilaria
authors.initials: I
authors.lastname: Scognamiglio
authors.forename: Stefano
authors.initials: S
authors.lastname: Alcaro
authors.forename: Anna
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authors.lastname: Artese
authors.forename: Francesco
authors.initials: F
authors.lastname: Ortuso
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Marina
authors.initials: M
authors.lastname: Sala
authors.forename: Pietro
authors.initials: P
authors.lastname: Campiglia