Chiral Heterocyclic Analogues with anti-HBV inhibition potency against viral RNaseH

Postgraduate Thesis uoadl:3328672 40 Read counter

Κατεύθυνση Φαρμακευτική Χημεία
Library of the School of Science
Deposit date:
Makri Maria
Supervisors info:
Γρηγόρης Ζωίδης, Αναπληρωτής Καθηγητής Τμήμα Φαρμακευτικής ΕΚΠΑ,
Λουγιάκης Νικόλαος Επίκ. Καθηγητής Τμήμα Φαρμακευτικής ΕΚΠΑ,
Μυριανθόπουλος Βασίλειος Επίκ. Καθηγητής Τμήμα Φαρμακευτικής ΕΚΠΑ
Original Title:
Ετεροκυκλικά Χηλικά Συμπλεκτικά Ανάλογα με αντι-HBV Δράση Μέσω Αναστολής της RNaseH του Ιού
Translated title:
Chiral Heterocyclic Analogues with anti-HBV inhibition potency against viral RNaseH
Hepatitis B virus (HBV) chronically infects more than 250.000 people and leads to the death of 820.000 patients annually. Commercially available antiviral drugs for the treatment of HBV are incapable of eliminating the infection and they cannot reduce completely the disease. These include nucleos(t)ide and interferon α analogues. The first ones constitute drugs of choice inhibiting HBV reverse transcriptase (RT), a domain of HBV polymerase necessary for replication of the viral genome. However, patients need to take them for life to have a normal life. Consequently, the research of this thesis is directed towards the development of inhibitors of the other important enzymatic function of HBV polymerase, that of ribonuclease H (RNaseH). It is an unexplored and promising area of Hepatitis B and many published potential inhibitors have demonstrated significant antiviral potency in a micromolar and nanomolar range against viral replication in cancer cell lines. Previous research has reported α-hydroxytropolone inhibitors, N-hydroxyimides as well as natural products. The present research focuses on N-hydroxypyrimidinediones and a new scaffold inspired by the active pharmaceutical substance minoxidil. Thus, their effectiveness against virus replication in vitro is evaluated, followed by structure-activity relationship studies that will be a valuable tool for future development of potent RNaseH inhibitors. Finally, the experimental synthetic routes of the designed molecules are discussed.
Main subject category:
Other subject categories:
Health Sciences
Medicinal Chemistry, inhibitor, Hepatitis B, RNaseH, chiral complexes, synthesis
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Μαρία Μακρή Final.pdf
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File access is restricted until 2026-05-26.