Unit:
Κατεύθυνση Σχεδιασμός και Ανάπτυξη νέων Φαρμακευτικών Ενώσεων - Φαρμακευτική ΧημείαLibrary of the School of Science
Supervisors info:
Εμμανουήλ Μικρός, Καθηγητής, Τμήμα Φαρμακευτικής ΕΚΠΑ,
Ι. Κωστάκης Επίκ. Καθηγητής Τμήμα Φαρμακευτικής ΕΚΠΑ,
Π. Μαράκος Καθηγητής Τμήμα Φαρμακευτικής ΕΚΠΑ
Original Title:
ΣΧΕΔΙΑΣΜΟΣ ΚΑΙ ΣΥΝΘΕΣΗ ΑΝΑΛΟΓΩΝ ΤΟΥ ΑΛΚΑΛΟΕΙΔΟΥΣ FLINDERSINE ΩΣ ΠΙΘΑΝΩΝ ΑΝΑΣΤΟΛΕΩΝ ΚΙΝΑΣΩΝ
Translated title:
DESIGN AND SYNTHSESIS OF FLINDERSINE ANALOGUES AS POTENTIAL KINASE INHIBITORS
Summary:
Protein kinases play a pivotal role in signal transduction and regulation of numerous cellular processes. Dysregulation or overexpression of kinases are involved in many diseases including malignancies, diabetes, autoimmune disorders etc. Therefore, the regulation of kinases’ expression seems to be of high importance as a therapeutic approach against the conditions mentioned above. DYRK1A, a serine/threonine kinase, plays critical role in brain development, whereas DYRK1A overexpression is correlated with several neurological disorders (Alzheimer & Parkinson). Abnormal expression of same superfamily kinases such as PIM-1, CLK1, CLK4 and GSK3B as well as other less studied kinases (GAK και GSG2) is correlated with several diseases such as oncogenesis and diabetes. Thus, developing inhibitors against kinases mentioned above is an interesting therapeutic approach. Our group has previously reported that Flindersine, a pyranoquinoline alkaloid, shows notable activity against DYRK1A. This observation was followed by synthesis of new spiro -flindersine analogues as to further study structure–activity relationships. This project is focused on studying the interactions between flindersine analogues synthesized during previous projects and DYRK1A active site as well as the synthesis of new flindersine analogues which would hopefully be more potent against DYRK1A. Additionally an attempt was made to predict the Flindersine pose inside DYRK1A active site, through comparison between pharmacological data and in-silico simulations. The pharmacological evaluation of flindersine analogues synthesized by our research group till this project, showed remarkable affinity with other kinases too like PIM-1. The results are encouraging and are guiding us to further study flindersine analogues as kinase inhibitors.
Main subject category:
Science
Other subject categories:
Health Sciences
Keywords:
flindersine,kinases,inhibitors,crystallography,PIM1,DYRK1A
File:
File access is restricted until 2026-05-26.
Zagouri.pdf
4 MB
File access is restricted until 2026-05-26.
