Synthesis, characterization and biological evaluation of (99m)Tc/Re-tricarbonyl quinolone complexes

• Published in: Journal of inorganic biochemistry 2016-07, Vol.160, p.94-105
• Main Authors: Kydonaki, Theocharis E, Tsoukas, Evangelos, Mendes, Filipa, Hatzidimitriou, Antonios G, Paulo, António, Papadopoulou, Lefkothea C, Papagiannopoulou, Dionysia, Psomas, George
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Neoplasm - chemistry; Binding Sites; Cattle; Contrast Media - chemical synthesis; Contrast Media - pharmacokinetics; Coordination Complexes - chemical synthesis; Coordination Complexes - pharmacokinetics; Crystallography, X-Ray; DNA - chemistry; DNA Topoisomerases, Type II - chemistry; DNA-Binding Proteins - antagonists & inhibitors; DNA-Binding Proteins - chemistry; Ethidium - chemistry; Fluoroquinolones - chemistry; Humans; Imidazoles - chemistry; Intercalating Agents - chemical synthesis; Intercalating Agents - pharmacokinetics; K562 Cells; Kinetics; Methanol - chemistry; Mice; Organophosphorus Compounds - chemistry; Oxolinic Acid - chemistry; Protein Binding; Quinolones - chemistry; Rhenium - chemistry; Serum Albumin - chemistry; Technetium - chemistry
• ISSN: 1873-3344
• DOI: 10.1016/j.jinorgbio.2015.12.010

New rhenium(I) tricarbonyl complexes with the quinolone antimicrobial agents oxolinic acid (Hoxo) and enrofloxacin (Herx) and containing methanol, triphenylphosphine (PPh3) or imidazole (im) as unidentate co-ligands, were synthesized and characterized. The crystal structure of complex [Re(CO)3(oxo)(PPh3)]∙0.5MeOH was determined by X-ray crystallography. The deprotonated quinolone ligands are bound bidentately to rhenium(I) ion through the pyridone oxygen and a carboxylate oxygen. The binding of the rhenium complexes to calf-thymus DNA (CT DNA) was monitored by UV spectroscopy, viscosity measurements and competitive studies with ethidium bromide; intercalation was suggested as the most possible mode and the DNA-binding constants of the complexes were calculated. The rhenium complex [Re(CO)3(erx)(im)] was assayed for its topoisomerase IIα inhibition activity and was found to be active at 100μM concentration. The interaction of the rhenium complexes with human or bovine serum albumin was investigated by fluorescence emission spectroscopy (through the tryptophan quenching) and the corresponding binding constants were determined. The tracer complex [(99m)Tc(CO)3(erx)(im)] was synthesized and identified by comparative HPLC analysis with the rhenium analog. The (99m)Tc complex was found to be stable in solution. Upon injection in healthy mice, fast tissue clearance of the (99m)Tc complex was observed, while both renal and hepatobiliary excretion took place. Preliminary studies in human K-562 erythroleukemia cells showed cellular uptake of the (99m)Tc tracer with distribution primarily in the cytoplasm and the mitochondria and less in the nucleus. These preliminary results indicate that the quinolone (99m)Tc/Re complexes show promise to be further evaluated as imaging or therapeutic agents.