Unit:
Κατεύθυνση Φαρμακευτική ΧημείαLibrary of the School of Science
Author:
Moianos Dimitrios
Supervisors info:
Γρηγόρης Ζωίδης, Αναπληρωτής Καθηγητής, Τμήμα Φαρμακευτικής, ΕΚΠΑ.,
Λουγιάκης Νικόλαος, Επίκουρος Καθηγητής Τμήμα Φαρμακευτικής, ΕΚΠΑ.,
Μυριανθόπουλος Βασίλειος, Επίκουρος Καθηγητής Τμήμα Φαρμακευτικής, ΕΚΠΑ.,
Original Title:
Σχεδιασμός, Σύνθεση και Βιολογική Αξιολόγηση Νέων Ετεροκυκλικών Χηλικών Συμπλεκτικών Αναλόγων με αντι-HBV Δράση μέσω Αναστολής της RNaseH του Ιού
Translated title:
Design, Synthesis and Biological Evaluation of Novel Heterocyclic Metal-Chelating Agents with anti-HBV Activity through Inhibition of the Viral RNaseH
Summary:
Hepatitis B virus (HBV) poses a significant challenge, affecting over 250,000 individuals annually and resulting in approximately 820,000 deaths. Despite available antiviral drugs like nucleos(t)ide analogues and interferon α (IFN-α) analogues, complete eradication or substantial mitigation of this chronic infection remains elusive. Nucleos(t)ide analogues, the drugs of choice, target the viral reverse transcriptase, an essential element of HBV polymerase, crucial for viral replication. However, these necessitate lifelong administration for patients to sustain an acceptable quality of life. This thesis concentrates on developing inhibitors for another crucial enzymatic component of HBV polymerase: the ribonuclease H (RNaseH). This area of inhibiting HBV RNase H remains largely unexplored but holds great promise in combating hepatitis B infection. Several potential inhibitors with activity in the order of μM and nM against viral replication in cancer cell lines have been reported in previous studies by our group and others. These include compounds from diverse chemical categories like α-hydroxytropolones, N-hydroxyimides, and certain natural products. Present research centers on the design and synthesis of novel N-hydroxypyridinediones (HPDs) encompassing varied side chain substituents (oxime and imine analogues). Additionally, two new scaffolds are explored—one inspired by the pharmacophore of the established drug minoxidil, while the other draws inspiration from the barbituric acid pharmacophore. Subsequently, these compounds are subjected to rigorous in vitro experiments to evaluate their efficacy against virus replication. These findings unveil crucial structure-activity relationships, offering invaluable insights that will propel the search for potent RNase H inhibitors.
Main subject category:
Science
Keywords:
Hepatitis B, HBV, antiviral agents, RNaseH
Number of references:
132
File:
File access is restricted until 2027-05-21.
Διπλωματική Εργασία-Μοϊάνος Δημήτριος_all corrections_final.pdf
4 MB
File access is restricted until 2027-05-21.
