Methodologies for Synthesis of Bioactive Compounds and Study of their Antitumor Activity and Inhibitory Activity Against the Main Protease of SARS-CoV-2

Doctoral Dissertation uoadl:3421759 18 Read counter

Unit:
Department of Chemistry
Library of the School of Science
Deposit date:
2024-10-30
Year:
2024
Author:
Theodoropoulou Maria
Dissertation committee:
Γεώργιος Κόκοτος, Καθηγητής, Τμήμα Χημείας, ΕΚΠΑ
Βικτώρια Μαγκριώτη, Αναπληρώτρια Καθηγήτρια, Τμήμα Χημείας, ΕΚΠΑ
Παναγιώτης Πολίτης, Ερευνητής Β’, Ίδρυμα Ιατροβιολογικών Ερευνών Ακαδημίας Αθηνών
Δημήτρης Γεωργιάδης, Καθηγητής, Τμήμα Χημείας, ΕΚΠΑ
Μαρία Κουφάκη, Διευθύντρια Ερευνών, Εθνικό Ίδρυμα Ερευνών
Εμμανουήλ Μικρός, Καθηγητής, Τμήμα Φαρμακευτικής, ΕΚΠΑ
Νικολαΐς Πουλή, Καθηγήτρια, Τμήμα Φαρμακευτικής, ΕΚΠΑ
Original Title:
Μεθοδολογίες Σύνθεσης Βιοδραστικών Ενώσεων και Μελέτη της Αντικαρκινικής Δράσης τους και της Ανασταλτικής τους Δράσης Έναντι της Κύριας Πρωτεάσης του SARS-CoV-2
Languages:
Greek
English
Translated title:
Methodologies for Synthesis of Bioactive Compounds and Study of their Antitumor Activity and Inhibitory Activity Against the Main Protease of SARS-CoV-2
Summary:
In this PhD thesis, a photocatalytic protocol for the reaction of N,N-dimethylanilines and N-substituted maleimides was initially studied. In particular, the reaction in question was carried out without the use of metal complexes, instead employing benzaldehyde as a photoinitiator and using simple household lamps as a light source. Tetrahydro-pyrrolo[3,2-c]quinolines resulting from this reaction could be precursors of compounds of pharmacological interest.
Histone deacetylases (HDACs) are enzymes capable of deacetylating lysine residues inhibiting the process of transcription. However, their abnormal activity has been associated with various pathological conditions. Mainly, their role in the development and progression of various malignancies is prominent. In this thesis, synthesis of compounds with potential anticancer activity was carried out. Initially, some benzothiazole derivatives were synthesized. A hydroxamic acid was also synthesized, along with a series of N-(2-aminophenyl)-benzamides. Subsequently, the ability of these compounds to inhibit the proliferation of cancer cells was studied. In particular, three cancer cell lines (A549, SF268 and Caco-2) were used in this study.
At the end of 2019, a new infectious respiratory disease emerged, the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The emergence of SARS-CoV-2 highlighted the need to find effective treatments against COVID-19. In this PhD thesis, inhibitors of the main protease (Mpro) of the virus were synthesized. In more detail, a series of 2-oxoamides was initially synthesized to conduct a structure-activity relationship study against Mpro. Finally, a nitroalkene, as well as some thiazolyl ketones, inhibitors of Mpro, were designed and synthesized.
Main subject category:
Science
Keywords:
inhibitors, anti-cancer activity, hydroxamic acid, benzamides, SARS-CoV-2, main protease, thiazolyl ketones
Index:
Yes
Number of index pages:
34
Contains images:
Yes
Number of references:
437
Number of pages:
339
File:
File access is restricted until 2029-10-30.

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