Synthesis of hydroxytyrosol/4-thiatocopherol hybrids, as proteasome activators

Postgraduate Thesis uoadl:2768764 457 Read counter

Unit:
Κατεύθυνση Σχεδιασμός και Ανάπτυξη νέων Φαρμακευτικών Ενώσεων - Φαρμακευτική Χημεία
Library of the School of Science
Deposit date:
2018-06-12
Year:
2018
Author:
Chazapi Evanthia
Supervisors info:
Καλογεροπούλου Θεοδώρα, Διευθύντρια ερευνών, Ινστιτούτο Βιολογίας Φαρμακευτικής Χημείας και Βιοτεχνολογίας, Εθνικό Ίδρυμα Ερευνών
Ανδρέας Τσοτίνης, Καθηγητής, Τμήμα Φαρμακευτικής, ΕΚΠΑ
Ιωάννης Παπαναστασίου, Επίκουρος Καθηγητής, Τμήμα Φαρμακευτικής, ΕΚΠΑ
Original Title:
Υβριδικές ενώσεις 4-θειατοκοφερόλης/υδρόξυτυροσόλης ενεργοποιητές του πρωτεασώματος
Languages:
Greek
Translated title:
Synthesis of hydroxytyrosol/4-thiatocopherol hybrids, as proteasome activators
Summary:
The present thesis involves the design and synthesis of new bio-inspired hydroxytyrosol/4-thiatocopherol hybrids.
The design of these analogues was based on previous studies of the research group of the Institute of Biology, Medicinal Chemistry and Biotechnology of the National Hellenic Research Foundation.
The aim of the work was the synthesis of novel compounds that can activate 20S proteasome and thus, may have a beneficial or therapeutic effect against human aging and/or in age related diseases and conditions.
In the context of the present study 5 new hybrid compounds were synthesized that combine hydroxytyrosol, which is the main antioxidant phenolic constituent of olive oil and structural component of oleuropein and 4-thiatocopherol which is a bioisostere of the chroman ring of tocopherol. The two subunits were connected by five-membered heterocycle rings which are either bioisosteres of the amide or ester bond or pharmacophores.
The biological evaluation of the new compounds was performed by Dr. Niki Chondrogiannis' research team by Ph.D. candidate Nikole Papaevgeniou at the Institute of Biology, Medicinal Chemistry and Biotechnology of the National Hellenic Research Foundation. The effect of the novel compounds on the chymotrypsin proteasome activation in young primary HFL-1 fibroblasts was examined.
The experiments showed proteasome activation at similar level by the compounds that are substituted by a 1,2,3-triazole, a 1,2,4-oxadiazole and a 1,3,4-oxadiazole ring at a concentration of 0.5 μg/mL. The least active compound at concentration of 0.5 μg / mL is the isoxazole ring-substituted derivative.
Main subject category:
Science
Keywords:
activators, proteasome, hydroxytyrosol, 4-thiatocopherol, oleuropein, bioisosteres
Index:
Yes
Number of index pages:
10
Contains images:
Yes
Number of references:
37
Number of pages:
184
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