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

The complex fac-[Re(C0)(3)(phendione)C1] (1) (where phendione = 1,10-phenanthroline-5,6-dione) has been synthesized and fully characterized by UV-visible, FUR, 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(C0)(5)CI] 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)(5)Cl] is a better PAF inhibitor than both the phendione ligand and I. Moreover, for the first time it is indicated that [Re(C0)(5)Cl], 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. (C) 2014 Elsevier Inc. All rights reserved.