Supervisors info:
Kωνσταντίνος Μεθενίτης, Αναπληρωτής Καθηγητής, Τμήμα Χημείας, Σχολή Θετικών Επιστημών
Original Title:
Σύνθεση και χαρακτηρισμός συμπλόκου Cu(II) με γλυκοζυλιωμένο παράγωγο της 2,9-(διμεθυλο)-1,10-φαινανθρολίνης (PDGluc). Μελέτη της αλληλεπίδρασης με CT-DNA και in vitro αξιολόγηση της βιολογικής του δράσης.
Translated title:
Synthesis and characterization of Cu (II) complex with glycosylated derivative of 2,9- (dimethyl) -1,10-phenanthroline (PDGluc). Study of interaction with CT-DNA and in vitro evaluation of its biological activity
Summary:
The present work is my thesis on the synthesis and characterization of Cu (II) complex with derivative of 2,9 dimethyl-1,10 phenanthroline, study of their interaction with CT-DNA and in vitro exploration of their biological activity as a possible new anticancer agent. The corresponding Cu(II) complex was successfully synthesized and fully characterized by various spectroscopic methods (IR, EPR, NMR, MS, UV-vis). This complex is expected to be equally characterized by selective anticancer action of 1,10-phenanthroline in conjuction with the cytotoxicity of metallic center, targeting synergistic effectiveness. These metal complexes are designed with the method drug targeted delivery (DTD). According to this method, the initial ligand has a certain molecular group which is capable of delivering it to the targeted cell avoiding accumulation to healthy cells. In addition, this specific group gives to the ligand and the metal complex of it new characteristic properties. In this study, the group that was chosen for the modulation of the ligand is glucose, a saccharide which gives to the initial molecule the desirable properties. Moreover, glucose as a sugar tends to interact with the DNA through its minor or major grooves (Groove Binding Affinity). In addition, their binding to CT-DNA was also been evaluated by UV-Vis spectroscopy, fluorescence, circular dichroism and viscometry. The PDGluc ligand interacts with CT-DNA in more than one way. Initially, for small ratios, the most likely interaction is groove binding. For larger ratios, however, some kind of intercalation with the DNA molecule is suggested. On the other hand, at the Cu(II) -PDGluc complex only the classical or partial intercalation appears. In terms of cytotoxicity, both the unblocked PDGluc and the Cu (II) -PDGluc complex showed a significant selectivity in the hormone-dependent human prostate cancer cell line LNCaP. In particular, the cytotoxicity recorded for the Cu (II) -PDGluc complex in the LNCaP cell line has excellent results, similar to Cisplatin.
Keywords:
1,10- phenanthroline, copper (II), glucose, DNA, anticancer activity
