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.