Production of reactive oxygen and nitrogen species by light irradiation of a nitrosyl phthalocyanine ruthenium complex as a strategy for cancer treatment.

Production of reactive oxygen species has been used in clinical therapy for cancer treatment in a technique known as Photodynamic Therapy (PDT). The success of this therapy depends on oxygen concentration since hypoxia limits the formation of reactive oxygen species with consequent clinical failure of PDT. Herein, a possible synergistic effect between singlet oxygen and nitric oxide (NO) is examined since this scenario may display increased tumoricidal activity. To this end, the trinuclear species [Ru(pc)(pz)2{Ru(bpy)2(NO)}2](PF6)6 (pc = phthalocyanine; pz = pyrazine; bpy = bipyridine) was synthesized to be a combined NO and singlet oxygen photogenerator. Photobiological assays using at 4 × 10(-6) M in the B16F10 cell line result in the decrease of cell viability to 21.78 ± 0.29% of normal under light irradiation at 660 nm. However, in the dark and at the same concentration of compound , viability was 91.82 ± 0.37% of normal. The potential application of a system like in clinical therapy against cancer may be as an upgrade to normal photodynamic therapy.

Biological nitric oxide signalling: chemistry and terminology.

Biological nitrogen oxide signalling and stress is an area of extreme clinical, pharmacological, toxicological, biochemical and chemical research interest. The utility of nitric oxide and derived species as signalling agents is due to their novel and vast chemical interactions with a variety of biological targets. Herein, the chemistry associated with the interaction of the biologically relevant nitrogen oxide species with fundamental biochemical targets is discussed. Specifically, the chemical interactions of nitrogen oxides with nucleophiles (e.g. thiols), metals (e.g. hemeproteins) and paramagnetic species (e.g. dioxygen and superoxide) are addressed. Importantly, the terms associated with the mechanisms by which NO (and derived species) react with their respective biological targets have been defined by numerous past chemical studies. Thus, in order to assist researchers in referring to chemical processes associated with nitrogen oxide biology, the vernacular associated with these chemical interactions is addressed.

A new nitrosyl ruthenium complex: synthesis, chemical characterization, in vitro and in vivo antitumor activities and probable mechanism of action.

This study describes the synthesis of a new ruthenium nitrosyl complex with the formula [RuCl(2)NO(BPA)] [BPA = (2-hydroxybenzyl)(2-methylpyridyl)amine ion], which was synthesized and characterized by spectroscopy, cyclic voltammetry, X-ray crystallography, and theoretical calculation data. The biological studies of this complex included in vitro cytotoxic assays, which revealed its activity against two different tumor cell lines (HeLa and Tm5), with efficacy comparable to that of cisplatin, a metal-based drug that is administered in clinical treatment. The in vivo studies showed that [RuCl(2)NO(BPA)]is effective in reducing tumor mass. Also, our results suggest that the mechanism of action of [RuCl(2)NO(BPA)] includes binding to DNA, causing fragmentation of this biological molecule, which leads to apoptosis.

Pt(II) and Ag(I) complexes with acesulfame: crystal structure and a study of their antitumoral, antimicrobial and antiviral activities.

Two new complexes of platinum(II) and silver(I) with acesulfame were synthesized. Acesulfame is in the anionic form acesulfamate (ace). The structures of both complexes were determined by X-ray crystallography. For K(2)[PtCl(2)(ace)(2)] the platinum atom is coordinated to two Cl(-) and two N-acesulfamate atoms forming a trans-square planar geometry. Each K(+) ion interacts with two oxygen atoms of the S(O)(2) group of each acesulfamate. For the polymeric complex [Ag(ace)](n) the water molecule bridges between two crystallographic equivalent Ag1 atoms which are related each other by a twofold symmetry axis. Two Ag1 atoms, related to each other by a symmetry centre, make bond contact with two equivalent oxygen atoms. These bonds give rise to infinite chains along the unit cell diagonal in the ac plane. The in vitro cytotoxic analyses for the platinum complex using HeLa (human cervix cancer) cells show its low activity when compared to the vehicle-treated cells. The Ag(I) complex submitted to in vitro antimycobacterial tests, using the Microplate Alamar Blue (MABA) method, showed a good activity against Mycobacterium tuberculosis, responsible for tuberculosis, with a minimal inhibitory concentration (MIC) value of 11.6microM. The Ag(I) complex also presented a promising activity against Gram negative (Escherichia coli and Pseudomonas aeruginosa) and Gram positive (Enterococcus faecalis) microorganisms. The complex K(2)[PtCl(2)(ace)(2)] was also evaluated for antiviral properties against dengue virus type 2 (New Guinea C strain) in Vero cells and showed a good inhibition of dengue virus type 2 (New Guinea C strain) replication at 200microM, when compared to vehicle-treated cells.

Lithium thiazolidine-4-carboxylate: synthesis, spectroscopic characterization and preliminary in vitro cytotoxic studies in human HeLa cells.

A new water-soluble lithium salt of thiazolidine-4-carboxylic acid was synthesized and characterized by chemical and spectroscopic techniques. Elemental and mass spectrometric (ESI-MS) analyses of the solid compound fit to the composition LiC(4)H(6)NSO(2). (1)H, (13)C nuclear magnetic resonance (NMR), [(1)H-(15)N] NMR and infrared (IR) analyses permitted to elucidate the structure of the compound. Biological activity was evaluated by cytotoxic analysis using HeLa cells. Determination of cell death was assessed using a tetrazolium salt colorimetric assay, which reflects the cells viability.

Participation of kallikrein-kinin system in different pathologies.

The general description of kinins refers to these peptides as molecules involved in vascular tone regulation and inflammation. Nevertheless, in the last years a series of evidences has shown that local hormonal systems, such as the kallikrein-kinin system, may be differently regulated and are of pivotal importance to pathophysiological control. The combined interpretations of many recent studies allow us to conclude that the kallikrein-kinin system plays broader and richer roles than those classically described until recently. In this review, we report findings concerning the participation of the kallikrein-kinin system in inflammation, cancer, and in pathologies related to cardiovascular, renal and central nervous systems.