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) 5 Cl] 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 enzymes 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 1.Moreover, for the first time it is indicated that [Re(CO) 5 Cl], with a IC 50 of 17 nM is comparable to the widely used PAF receptor antagonists, BN52021 and WEB2170 with IC 50 of 30 and 20 nM, respectively, whereas 1 affects PAF-catabolism.

A Review on Platelet Activating Factor Inhibitors: Could a New Class of Potent Metal-Based Anti-Inflammatory Drugs Induce Anticancer Properties?

“…Kaplanis and coworkers [142] reported on a Re(I) derivative (Figure 8) of the general type fac -[Re(phendione)(CO) 3 Cl] ( Re-1 ) (where phendione = 1,10-phenanthroline-5,6-dione) that has been evaluated as inhibitor of PAF-induced aggregation of washed rabbit platelets (IC 50 = 0.86  μ M).…”

Metal complexes as potential modulators of inflammatory and autoimmune responses

“…14). 51 Additionally, complex 41 and [Re(CO 5 )Cl] showed activity against PAF-basic metabolic enzyme activities in rabbit leukocyte homogenates. In cellular proliferation studies, the free ligand phendione was found to be highly cytotoxic towards a range of cancer cell lines, but this toxicity was markedly reduced upon complexation to Re( i ).…”

Crystal structure of (E)-2-(((1,10-phenanthrolin-5-yl)imino)methyl)-5-methylphenol monohydrate, C20H15N3O·H2O

“…It is hydrophobic and can behave as a π-acceptor chelator despite the poor σ-donor capability of the heteroaromatic nitrogen atoms [3]. Phen has further distinct chemical advantages, as its planarity allows phen complexes to intercalate with DNA and RNA via aromatic π-stacking [6]. In addition, the photochemical and photophysical properties of phen-based complexes has found application in catalysis, luminescent materials and bio-medical elds [7][8][9].…”