pH-Sensitive Gold Nanorods for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Delivery and DNA-Binding Studies.

A facile experimental protocol for the synthesis of poly(ethylene glycol)-modified (PEGylated) gold nanorods (AuNRs@PEG) is presented as well as an effective drug loading procedure using the non-steroidal anti-inflammatory drug (NSAID) naproxen (NAP). The interaction of AuNRs@PEG and drug-loaded AuNRs (AuNRs@PEG@NAP) with calf-thymus DNA was studied at a diverse temperature revealing different interaction modes; AuNRs@PEG may interact via groove-binding and AuNRs@PEG@NAP may intercalate to DNA-bases. The cleavage activity of the gold nanoparticles for supercoiled circular pBR322 plasmid DNA was studied by gel electrophoresis while their affinity for human and bovine serum albumins was also evaluated. Drug-release studies revealed a pH-sensitive behavior with a release up to a maximum of 24% and 33% NAP within the first 180 min at pH = 4.2 and 6.8, respectively. The cytotoxicity of AuNRs@PEG and AuNRs@PEG@NAP was evaluated against MCF-7 and MDA-MB-231 breast cancer cell lines. The development of AuNRs as an efficient non-steroidal anti-inflammatory drugs (NSAIDs) delivery system for chemotherapy is still in its infancy. The present work can shed light and inspire other research groups to work in this direction.

Metal(II) Complexes of the Fluoroquinolone Fleroxacin: Synthesis, Characterization and Biological Profile.

A series of complexes of divalent transition metals (Cu(II), Mn(II), Zn(II), Co(II) and Ni(II)) with the quinolone antibacterial agent fleroxacin, in the absence or presence of an α-diimine such as 2,2'-bipyridine, 1,10-phenanthroline or 2,2'-bipyridylamine, were prepared and characterized. The complexes were characterized by various physicochemical and spectroscopic techniques and by single-crystal X-ray crystallography. The in vitro antibacterial activity of the complexes was studied against the bacterial strains Staphylococcus aureus, Bacillus subtilis and Xanthomonas campestris and was higher than that of free quinolone. The affinity of the complexes for bovine and human serum albumin was studied by fluorescence emission spectroscopy and the determined binding constants showed tight and reversible binding to the albumins. The interaction of the complexes with calf-thymus DNA was studied by various techniques, which showed that intercalation was the most plausible mode of interaction.

Copper(II) complexes with non-steroidal anti-inflammatory drugs: Structural characterization, in vitro and in silico biological profile.

Six novel copper(II) complexes with the non-steroidal anti-inflammatory drugs ibuprofen, loxoprofen, fenoprofen and clonixin as ligands were synthesized and characterized by diverse techniques including single-crystal X-ray crystallography. The in vitro scavenging activity of the complexes against 1,1-diphenyl-picrylhydrazyl and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) free radicals and the ability to reduce H2O2 were studied in the context of the antioxidant activity studies. The complexes may interact with calf-thymus DNA via intercalation as revealed by the techniques employed. The affinity of the complexes for bovine and human serum albumins was evaluated by fluorescence emission spectroscopy and the corresponding binding constants were determined. Molecular docking simulations on the crystal structure of calf-thymus DNA, human and bovine serum albumins were also employed in order to study in silico the ability of the studied compounds to bind to these target biomacromolecules, in terms of impairment of DNA and transportation through serum albumins, to explain the observed in vitro activity and to establish a possible mechanism of action.

Synthesis, characterization and (in vitro and in silico) biological activity of a series of dioxouranium(VI) complexes with non-steroidal anti-inflammatory drugs.

The reaction of the dioxouranium(VI) ion with a series of non-steroidal anti-inflammatory drugs (NSAIDs), namely mefenamic acid, indomethacin, diclofenac, diflunisal and tolfenamic acid, as ligands in the absence or presence of diverse N,N'-donors (1,10-phenanthroline,2,2'-bipyridine or 2,2'-bipyridylamine) as co-ligands led to the formation of ten complexes bearing the formulas [UO2(NSAID-O,O')2(O-donor)2] or [UO2(NSAID-O,O')2(N,N'-donor)], respectively. The complexes were characterized with diverse spectroscopic techniques and the crystal structures of three complexes were determined by single-crystal X-ray crystallography. The biological profile of the resultant complexes was assessed in vitro and in silico. The in vitro studies include their antioxidant properties (ability to scavenge free radicals 1,1-diphenyl-picrylhydrazyl and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and to reduce H2O2), their interaction with DNA (linear calf-thymus DNA or supercoiled circular pBR322 plasmid DNA) and their affinity for serum albumins (bovine and human serum albumin). In silico molecular docking calculations were performed regarding the behavior of the complexes towards DNA and their binding to both albumins.