Re(I) tricarbonyl complex of 1,10-phenanthroline-5,6-dione: DNA binding, cytotoxicity, anti-inflammatory and anti-coagulant effects towards platelet activating factor

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• 作者：Michael Kaplanis^a ; George Stamatakis^b ; Vasiliki D. Papakonstantinou^b ; Maria Paravatou-Petsotas^c ; Constantinos A. Demopoulos^b ; Christiana A. Mitsopoulou^a ; ^{cmitsop@chem.uoa.gr" class="auth_mail}
• 关键词：Re(I) carbonyl ; Phendione ; DNA binding ; DNA photocleavage ; Anticancer activity ; PAF-metabolism
• 刊名：Journal of Inorganic Biochemistry
• 出版年：June, 2014
• 年：2014
• 卷：135
• 期：Complete
• 页码：1-9
• 全文大小：816 K

文摘

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 17 nM is comparable to the widely used PAF receptor antagonists, BN52021 and WEB2170 with IC₅₀ of 30 and 20 nM, respectively, whereas 1 affects PAF-catabolism.