title: Re(I) tricarbonyl complex of 1,10-phenanthroline-5,6-dione: DNA binding, cytotoxicity, anti-inflammatory and anti-coagulant effects towards platelet activating factor.
abstract: The complex fac-[Re(CO)3(phendione)Cl] (1) (where phendione=1,10-phenanthroline-5,6-dione) has been synthesized and fully characterized by UV-visible, FTIR, and NMR techniques. The DNA binding properties of 1 are investigated by UV-spectrophotometric (melting curves), covalent binding assay, CV (cyclic voltammetry), circular dichroism (CD) and viscosity measurements. Experimental data indicate that 1 fits into the major groove without disrupting the helical structure of the B-DNA in contrast to the free phendione which intercalates within the base pairs of DNA. Upon irradiation, complex 1 promotes the cleavage of plasmid pBR322 DNA from supercoiled form I to nicked form II via a proton coupled electron transfer mechanism. This comes as a result of experimental data in anaerobic/aerobic conditions and in the presence of DMSO. The biological activities of 1 and its precursors [Re(CO)5Cl] and phendione are tested towards a series of cancerous cell lines as glioblastoma (T98G), prostate cancer (PC3) and breast cancer (MCF-7) as well as platelet activating factor (PAF)-aggregation. Moreover, all the aforementioned compounds are tested for their ability to modulate PAF-basic metabolic enzyme activities in preparations of rabbit leukolytes. The in vitro experiments indicate that phendione has a better antitumor effect than cisplatin whereas [Re(CO)5Cl] is a better PAF inhibitor than both the phendione ligand and 1. Moreover, for the first time it is indicated that [Re(CO)5Cl], with a IC50 of 17nM is comparable to the widely used PAF receptor antagonists, BN52021 and WEB2170 with IC50 of 30 and 20nM, respectively, whereas 1 affects PAF-catabolism.
authors.affiliation: Laboratory of Inorganic Chemistry, Faculty of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 157 71 Athens, Greece.
authors.forename: Michael
authors.initials: M
authors.lastname: Kaplanis
authors.affiliation: Laboratory of Biochemistry, Faculty of Chemistry, National and Kapodistrian University of Athens, Athens 15771, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Stamatakis
authors.affiliation: Laboratory of Biochemistry, Faculty of Chemistry, National and Kapodistrian University of Athens, Athens 15771, Greece.
authors.forename: Vasiliki D
authors.initials: VD
authors.lastname: Papakonstantinou
authors.affiliation: Institute of Nuclear and Radiological Sciences and Technology, Energy and Safety, National Centre for Scientific Research "Demokritos", 15310 Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Paravatou-Petsotas
authors.affiliation: Laboratory of Biochemistry, Faculty of Chemistry, National and Kapodistrian University of Athens, Athens 15771, Greece.
authors.forename: Constantinos A
authors.initials: CA
authors.lastname: Demopoulos
authors.affiliation: Laboratory of Inorganic Chemistry, Faculty of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 157 71 Athens, Greece. Electronic address: cmitsop@chem.uoa.gr.
authors.forename: Christiana A
authors.initials: CA
authors.lastname: Mitsopoulou
mesh_terms: D000327:Adsorption; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D000925:Anticoagulants / Q000737:chemistry / Q000494:pharmacology*; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D010618:Phenanthrolines / Q000737:chemistry / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D044366:Transition Temperature; D014783:Viscosity
chemical_list: D000893:Anti-Inflammatory Agents; D000925:Anticoagulants; D056831:Coordination Complexes; D010618:Phenanthrolines; D010972:Platelet Activating Factor; C000593532:tricarbonyl(1,10-phenanthroline-5,6-dione)rhenium(I); D004247:DNA; C427203:calf thymus DNA
keywords: Anticancer activity; DNA binding; DNA photocleavage; PAF-metabolism; Phendione; Re(I) carbonyl