ΠΜΣ με ειδίκευση ΑΠΟΜΟΝΩΣΗ, ΑΝΑΠΤΥΞΗ, ΠΑΡΑΓΩΓΗ ΚΑΙ ΕΛΕΓΧΟΣ ΒΙΟΔΡΑΣΤΙΚΩΝ ΦΥΣΙΚΩΝ ΠΡΟΪΟΝΤΩΝ
Library of the School of Science

2016-05-23

2016

Σπανού Δανάη

Αλέξιος-Λέανδρος Σκαλτσούνης Καθηγητής

Σχεδιασμός, νέες συνθετικές προσεγγίσεις και βιολογικοί στόχοι αναλόγων φλαβοπυριδόλης

Greek

Design, New synthetic approaches and Biological targets of Flavopiridol Analogues

Flavopiridol, a hemisynthetic flavone inspired from the natural product
rohitukine, is the first CDK inhibitor to enter clinical trials and has
recently been granted an Orphan Drug designation for the treatment of patients
with Acute Myeloid Leukemia. The unique scaffold of flavopiridol combines the
structural characteristics of flavonoids with some alkaloid properties and it
has been submitted to several modifications the past decades, aiming to
ameliorate the compound’s biological properties. However, the synthesized
derivatives had more than one features altered simultaneously and they were
less active than flavopiridol itself. These data, along with the demanding
synthetic path proposed, led us to design a series of analogues with only one
structural alteration each time and also, to investigate a simpler route for
their synthesis. Based on this rational, we synthesized derivatives with
differentiated either the alkaloid moiety or the substitution of the flavone’s
aromatic ring, while we achieved to establish a more efficient and less
expensive synthetic pathway. All the analogues, as well as some of the key
compounds for this synthesis, were evaluated in vitro for their cytotoxic
activity and their ability to inhibit Cyclin Dependent Kinases.

Flavopyridol, Flavoalkaloids, Kinases, Leukemia, CDKs

Yes

137-138

Yes

111

138

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https://pergamos.lib.uoa.gr/uoa/dl/object/1320267