Unit:
Κατεύθυνση Ανόργανη Χημεία και Εφαρμογές της στη ΒιομηχανίαLibrary of the School of Science
Author:
Magiakos Alexandros
Supervisors info:
Κωνσταντίνος Μεθενίτης, Αναπληρωτής Καθηγητής, Τμήμα Χημείας, ΕΚΠΑ
Original Title:
Σύνθεση και χαρακτηρισμός συμπλόκου του Ru(II) με το παράγωγο της 1,10-φαινανθρολίνης, 2,9-δι(αμινομέθυλο)-1,10-φαινανθρολίνη (PDAM), από το πρόδρομo cis-Ru(DMSO)4Cl2. Mελέτη της αλληλεπίδρασης του συμπλόκου με CT-DNA και την πρωτεΐνη BSA. In vitro αξιολόγηση της βιολογικής δράσης του συμπλόκου.
Translated title:
Synthesis and characterization of Ru(II) complex with the derivative of 1,10-phenanthroline, 2,9-(diaminomethyl)-1,10-phenanthroline (PDAM), from the precursor cis-Ru(DMSO)4Cl2. Study of its interaction with CT-DNA and the protein BSA. In vitro evaluation of the biological activity of the complex.
Summary:
The aim of the present thesis is the synthesis and characterization of Ru(II) complex with derivative of 1,10-phenanthroline (PDAM) from the precursor cis-Ru(DMSO)4Cl2 and study of its biological activity as potential new anticancer drug. The corresponding Ru(II) complex (cisRu-PDAM) was successfully synthesized and fully characterized by various spectroscopic techniques (IR, Fluorescence, NMR, UV-Vis, CD), showing selectivity in producing the enantiomer (Λ)-cisRu-PDAM. The selection of the ligand was made due to the interaction of 1,10-phenanthroline and its derivatives with DNA and proteins, showing significant biological activity as potential therapeutic agents by causing apoptosis to tumour cells and death to microorganisms and viruses. In addition, their complexation with transition metals is numerous and enhance their activity, whereas the development of labile complexes is of quite interest because of their well-known structures and characteristics (spectral, photochemical and electrochemical), which allow us the direct and detailed study of their interaction with biological systems. Hence, the interaction of cisRu-PDAM with CT-DNA and protein BSA (bovine serum albumin) was studied with the techniques of Circular Dichroism (CD), UV-Vis, Fluorescence and the hydrodynamic method of Viscometry. The data confirm the strong interaction of cisRu-PDAM with DNA, which appears to bind with more than one ways to it. The ways of interaction depend on the ratio R=[cisRu-PDAM]/[DNA]. Thus, at R<2 classical intercalation is proposed by simultaneous comformational change of DNA from B to A structure. At values of R>0,2 the complex binds to DNA in a way that bends its double strand. In the matter of BSA-complex interaction, binding in Sudlow site I was determined. The results show that the strength of binding, makes BSA a perfect carrier for the complex. Finally, in vitro exploration of biological activity of PDAM, the precursor and cisRu-PDAM against MCF-7 and PC-3 cancer cells with MTT assay, reveal stronger cytotoxic activity of the complex comparing to the free ligand and the precursor, quite similar to cis-platin.
Main subject category:
Science
Keywords:
1,10- phenanthroline, ruthenium (II), DNA, BSA (Serum Albumin), anticancer activity
Number of index pages:
20
Number of references:
243
