Unit:
Κατεύθυνση Σχεδιασμός και Ανάπτυξη νέων Φαρμακευτικών Ενώσεων - Φαρμακευτική ΧημείαLibrary of the School of Science
Supervisors info:
Ανδρέας Τσοτίνης, Καθηγητής στο Τμήμα Φαρμακευτικής
Παπαναστασίου Ιωάννης, Επίκουρος Καθηγητής στο Τμήμα Φαρμακευτικής
Καλογεροπούλου Θεοδώρα, Διευθύντρια Ερευνών, Εθνικό Ίδρυμα Ερευνών
Original Title:
Σύνθεση νέων νευροστεροειδών εν δυνάμει μιμητών των νευροτροφινών
Translated title:
Synthesis of novel neurosteroids mimicking neurotrophins
Summary:
The present dissertation involves the design and synthesis of new 17-spiro-dehydroepiandrosterone (DHEA) derivatives with the aim to evaluate the stereochemical requirements for neurotrophin mimetic activity.
The design of these analogues was based on previous findings of the research group of Dr Theodora Calogeropoulou, in collaboration with the group of Prof. Achileas Gravanis, which showed that 17-spiroepoxy analogues of dehydroepiandrosterone possess neuroprotective activity mimicking that of nerve growth factor (NGF), through their interaction with the TrkA receptor. More specifically, in the present work two series of C17-spiro derivatives were synthesized: one series encompasses C17-spiro-2,6-dehydropyran and C17-spiro-2,5-dehydrofouran analogues of DHEA and one series C17-spiro-cyclopropyl analogues. The key-reactions for the synthesis of 17-spiro heterocyclic rings were the ring closing ene and enyne metathesis, catalyzed by Grubbs’ catalyst 2nd generation, while for the cyclopropane derivatives the Simmons-Smith cyclopropanation reaction.
The aim of the work was to investigate the effect of the size and substitution of the spiro rings on the binding to neurotrophins’ receptors, as well as on the neuroprotective activity of the respective analogues. The biological evaluation is in progress.
Main subject category:
Science
Keywords:
neurosteroids, neurodegenerative diseases
