Synthesis, biological evaluation, and molecular modeling of oleuropein and its semisynthetic derivatives as cyclooxygenase inhibitors.
Oleuropein, the main phenolic compound in virgin olive oil, and several of its derivatives such as oleuropein aglycone, hydroxytyrosol, and their respective acetylated lipophilic forms were obtained by simple and environmentally friendly semisynthetic protocols. The same molecules were then tested in vitro and in vivo, comparing their intriguing anti-COX-1 and anti-COX-2 properties to those of well-known anti-inflammatory drugs such as ibuprofen and celecoxib. Finally, molecular modeling experiments displaying the most probable binding modes within the classical binding clefts of the enzymes suggest the heme moiety as a potential alternative target.
Procopio
Antonio
A
Dipartimento di Scienze Farmacobiologiche, Università Magna Graecia di Catanzaro, Complesso Nini Barbieri, 88021 Roccelletta di Borgia (CZ), Italy. procopio@unicz.it
Alcaro
Stefano
S
Nardi
Monica
M
Oliverio
Manuela
M
Ortuso
Francesco
F
Sacchetta
Paolo
P
Pieragostino
Damiana
D
Sindona
Giovanni
G
D001665:Binding Sites; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D057888:Iridoid Glucosides; D039823:Iridoids; D008968:Molecular Conformation; D031658:Olea / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry; D011451:Prostaglandin-Endoperoxide Synthases / Q000737:chemistry; D011485:Protein Binding; D011714:Pyrans / Q000138:chemical synthesis / Q000737:chemistry*
D016861:Cyclooxygenase Inhibitors; D057888:Iridoid Glucosides; D039823:Iridoids; D010936:Plant Extracts; D011714:Pyrans; C002769:oleuropein; D011451:Prostaglandin-Endoperoxide Synthases