Unit:
Department of ChemistryLibrary of the School of Science
Author:
Pagoni Aikaterini
Dissertation committee:
Βασιλείου Σταματία, Αναπληρώτρια Καθηγήτρια, ΕΚΠΑ
Βουγιουκαλάκης Γεώργιος, Αναπληρωτής Καθηγητής, ΕΚΠΑ
Γεωργιάδης Δημήτριος, Καθηγητής, ΕΚΠΑ
Γκιμήσης Αθανάσιος, Καθηγητής, ΕΚΠΑ
Μαγκριώτη Βικτώρια, Αναπληρώτρια Καθηγήτρια, ΕΚΠΑ
Μαυρομούστακος Θωμάς, Καθηγητής, ΕΚΠΑ
Στρατίκος Ευστράτιος, Αναπληρωτής Καθηγητής, ΕΚΠΑ
Original Title:
Σχεδιασμός, σύνθεση και βιολογικές μελέτες πολυφαινολικών παραγώγων
Translated title:
Design, synthesis and biological studies of polyphenolic derivatives
Summary:
The present thesis has two topics as research subjects. The first includes the synthesis of compounds against Alzheimer's disease, through the strategy of multi-target-directed ligand design. Using polyphenolic acids and lipoic acid as the parent compounds, as well as amino alcohols or diamines as linkers, hybrid molecules were synthesized and were studied for their physicochemical and biological properties. Ferulic acid derivative exhibited the highest antioxidant and neuroprotective activity, which, in combination with the stability of the compound, makes it a potent hybrid molecule.
The second subject of the thesis includes the synthesis of novel inhibitors against the enzyme urease. In this context, bifunctional molecules were synthesized, which interact simultaneously with both the Ni2+ ions (via a phosphonate/carboxylate system) and the sulfhydryl group of Cys322 (via a cation ring), in the active site of the enzyme. The inhibitors were studied for their inhibitory action on the enzyme, and molecular modeling experiments were performed to determine how they bind to the enzyme. 3-((1-(3,4-dihydroxyphenyl)-3-methoxy-3-oxopropyl)(hydroxy)phosphoryl)propanoic acid exhibited the strongest, irreversible inhibitory activity with kinact /KI = 10420 s-1 M-1.
Finally, in the same context, bifunctional urease inhibitors, based on the structure of urea, were also synthesized. Thus, urea, thiourea and carbamate catechol derivatives were prepared and studied for their inhibitory activity. 1-Cyclohexyl-3-(3,4-dihydroxybenzyl)urea exhibited the best inhibitory effect against the urease enzyme with IC50 = 571.7 mM.
Main subject category:
Science
Keywords:
Alzheimer's disease, polyphenolic acids, lipoic acid, hybrid compounds, urease, organophosphate compounds, urea, catechol
Number of index pages:
17
Number of references:
287
