Supervisors info:
Αλέξιος - Λέανδρος Σκαλτσούνης Kαθηγητής ΕΚΠΑ (επιβλέπων), Βασίλειος Ρούσσης Καθηγητής ΕΚΠΑ, Νεκτάριος Αληγιάννης Επίκ. Καθηγητής ΕΚΠΑ
Summary:
In recent years, numerous epidemiological studies have shown a weak effect of
cardiovascular and neurodegenerative disease, diabetes and cancer in the
Mediterranean region. This low incidence was attributed to the use of olive
oil, the principal characteristic of the Southern European diet. Oleuropein, a
phenolic secoiridoid glucoside, is the major constituent of Olea europaea
(Oleaceae) leaves and unprocessed olive drupes and is responsible for the
bitterness of olives.
In this work, we proposed to exploit this abundant raw material by providing
different hemisynthetic transformations, to improve biological activity and
study structure/ activity relations.
Accordingly, the hydroxylation degree of the hydroxytyrosol part has been
modified along with the length of the connecting chain. New alkyl esters, amide
and thioester derivatives have been synthesized by esterification/amidation of
oleoside 11-methylester tetraacetate, which was obtained by saponification of
oleuropein, followed by acetylation of the glucose part. The final selective
deprotection of the acetate was carried out by diethylamine.
Many studies have reported that oleuropein possesses a large range of
biological activities, including antioxidant, anti-hypertensive,
anti-inflammatory, anti-atherogenic, anti-cancer, anti-microbial and antiviral,
anti-aging, skin protectant and neuroprotective effects. Recently, oleuropein
has shown potential cardioprotective, anti-ischemic and hypolipidemic
activities. For these reasons, several formulations of olive extracts
containing up to 60% of oleuropein are commercially available as food
supplement.
Despite the plethora of pharmacological properties, oleuropein is not currently
used as active principle in drugs, because of its lack of specificity.
Therefore, in this work, we innovatively report the synthesis of natural and
non-natural oleuropein analogs with modification of the phenolic part. A new
chemical library of 60 derivatives has been created, all products have already
been tested on various cancer cell lines and results are presented.
Keywords:
Oleuropein, Oleuropein, Secoiridoids, Oleoside, Olea europaea
