Electrochemistry of chemotherapeutic alkylating agents and their interaction with DNA.

Alkylating agents were among the first anticancer drugs to be discovered and continue to be the most commonly used in chemotherapy. They are electrophiles that react with the ring nitrogen and extracyclic oxygen atoms of DNA bases, forming covalent adducts that further lead to cross-linking of DNA strands, abnormal base pairing or DNA strand breaks. The investigation and quantitative analysis of alkylating agents in biological samples are essential for monitoring the therapy progression and efficiency, understanding their pharmacokinetics and develop new more effective and specific chemotherapeutical drugs.

DNA Electrochemical Biosensors for In Situ Probing of Pharmaceutical Drug Oxidative DNA Damage.

Deoxyribonucleic acid (DNA) electrochemical biosensors are devices that incorporate immobilized DNA as a molecular recognition element on the electrode surface, and enable probing in situ the oxidative DNA damage. A wide range of DNA electrochemical biosensor analytical and biotechnological applications in pharmacology are foreseen, due to their ability to determine in situ and in real-time the DNA interaction mechanisms with pharmaceutical drugs, as well as with their degradation products, redox reaction products, and metabolites, and due to their capacity to achieve quantitative electroanalytical evaluation of the drugs, with high sensitivity, short time of analysis, and low cost. This review presents the design and applications of label-free DNA electrochemical biosensors that use DNA direct electrochemical oxidation to detect oxidative DNA damage.

Nanostructured material-based electrochemical sensing of oxidative DNA damage biomarkers 8-oxoguanine and 8-oxodeoxyguanosine: a comprehensive review.

Oxidative DNA damage plays an important role in the pathogenesis of various diseases. Among oxidative DNA lesions, 8-oxoguanine (8-oxoG) and its corresponding nucleotide 8-oxo-2'-deoxyguanosine (8-oxodG), the guanine and deoxyguanosine oxidation products, have gained much attention, being considered biomarkers for oxidative DNA damage. Both 8-oxoG and 8-oxodG are used to predict overall body oxidative stress levels, to estimate the risk, to detect, and to make prognosis related to treatment of cancer, degenerative, and other age-related diseases.

Natural phenolic antioxidants electrochemistry: Towards a new food science methodology.

Natural phenolic compounds are abundant in the vegetable kingdom, occurring mainly as secondary metabolites in a wide variety of chemical structures. Around 10,000 different plant phenolic derivatives have been isolated and identified. This review provides an exhaustive overview concerning the electron transfer reactions in natural polyphenols, from the point of view of their in vitro antioxidant and/or pro-oxidant mode of action, as well as their identification in highly complex matrixes, for example, fruits, vegetables, wine, food supplements, relevant for food quality control, nutrition, and health research.

Caveolin proteins electrochemical oxidation and interaction with cholesterol.

Caveolae consist in lipid raft domains composed of caveolin proteins, cholesterol, glycosphingolipids, and GPI-anchored proteins. Caveolin proteins present three different types, caveolin 1 (CAV-1), caveolin 2 (CAV-2) and caveolin 3 (CAV-3), with a very similar structure and amino acid composition. The native caveolin proteins oxidation mechanism was investigated for the first time, at a glassy carbon electrode, using cyclic, square wave and differential pulse voltammetry.

Electrochemical and AFM Characterization of G-Quadruplex Electrochemical Biosensors and Applications.

Guanine-rich DNA sequences are able to form G-quadruplexes, being involved in important biological processes and representing smart self-assembling nanomaterials that are increasingly used in DNA nanotechnology and biosensor technology. G-quadruplex electrochemical biosensors have received particular attention, since the electrochemical response is particularly sensitive to the DNA structural changes from single-stranded, double-stranded, or hairpin into a G-quadruplex configuration. Furthermore, the development of an increased number of G-quadruplex aptamers that combine the G-quadruplex stiffness and self-assembling versatility with the aptamer high specificity of binding to a variety of molecular targets allowed the construction of biosensors with increased selectivity and sensitivity.

Electrochemistry of Alzheimer Disease Amyloid Beta Peptides.

Alzheimer's disease (AD) is a widespread form of dementia that is estimated to affect 44.4 million people worldwide. AD pathology is closely related to the accumulation of amyloid beta (Aβ) peptides in fibrils and plagues, the small oligomeric intermediate species formed during the Aβ peptides aggregation presenting the highest neurotoxicity.

Pharmaceuticals released from senior residences: occurrence and risk evaluation.

One of the main pursuits, yet most difficult, in monitoring studies is to identify the sources of environmental pollution. In this study, we have identified health-care facilities from south European countries as an important source of pharmaceuticals in the environment. We have estimated that compounds consumed in by the elderly and released from effluents of senior residences can reach river waters at a concentration higher than 0.

Alzheimer's disease amyloid beta peptides in vitro electrochemical oxidation.

The oxidative behaviour of the human amyloid beta (Aβ and Aβ) peptides and a group of similar peptides: control inverse (Aβ and Aβ), mutants (AβPhe and AβNle), rat AβRat, and fragments (Aβ, Aβ, Aβ, Aβ, and Aβ), in solution or adsorbed, at a glassy carbon electrode, by cyclic and differential pulse voltammetry, were investigated and compared. Structurally the Aβ and Aβ sequences contain five electroactive amino acid residues, one tyrosine (Tyr), three histidines (His, His and His) and one methionine (Met). The Aβ peptide 3D structure influenced the exposure of the redox residues to the electrode surface and their oxidation peak currents.

Calcium-induced calmodulin conformational change. Electrochemical evaluation.

Calmodulin (CaM) is an essential protein present in all eukaryote cells, ranging from vertebrates to unicellular organisms. CaM is the most important Ca signalling protein, composed of two domains, N- and C-terminal domains, linked by a flexible central α-helix, and is responsible for the regulation of numerous calcium-mediated signalling pathways. Four calcium ions bind to CaM, changing its conformation and determining how it recognizes and regulates its cellular targets.

Amyloid-β peptides time-dependent structural modifications: AFM and voltammetric characterization.

The human amyloid beta (Aβ) peptides, Aβ1-40 and Aβ1-42, structural modifications, from soluble monomers to fully formed fibrils through intermediate structures, were investigated, and the results were compared with those obtained for the inverse Aβ40-1 and Aβ42-1, mutant Aβ1-40Phe(10) and Aβ1-40Nle(35), and rat Aβ1-40Rat peptide sequences. The aggregation was followed at a slow rate, in chloride free media and room temperature, and revealed to be a sequence-structure process, dependent on the physicochemical properties of each Aβ peptide isoforms, and occurring at different rates and by different pathways. The fibrilization process was investigated by atomic force microscopy (AFM), via changes in the adsorption morphology from: (i) initially random coiled structures of ∼0.

Flavonoids electrochemical detection in fruit extracts and total antioxidant capacity evaluation.

Phenolic compounds detection in fruit extracts from: açai, bacuri, buriti, blackberry, black mulberry, blueberry, juçara, physalis, raspberry, and tamarillo, have been performed by reverse-phase high performance liquid chromatography with electrochemical detection (RP-HPLC-EC), using two detectors in series: a wall-jet detector flow cell with a glassy carbon electrode, and a thin-layer flow cell detector with a boron doped diamond electrode. This methodology, in gradient elution mode, was successfully used to detect seventeen phenolic compounds in the fruit extracts. The total antioxidant capacity of the fruit extracts by the electrochemical quantitative index (EI) and the method of capture of diphenilpicrilhydrazil (DPPH(●)) free radical "efficient concentration" (EC50), was evaluated.

In situ dsDNA-bevacizumab anticancer monoclonal antibody interaction electrochemical evaluation.

The interaction of the anticancer monoclonal antibody bevacizumab (BEVA) with double-stranded DNA (dsDNA) was studied by voltammetry and gel-electrophoresis in incubated samples and using the dsDNA-electrochemical biosensor. The voltammetric results revealed a decrease and disappearance of the dsDNA oxidation peaks with increasing incubation time, showing that BEVA binds to the dsDNA but no DNA oxidative damage was detected electrochemically. Non denaturing agarose gel-electrophoresis experiments were in agreement with the voltammetric results showing the formation of compact BEVA-dsDNA adduct.

In situ electrochemical evaluation of dsDNA interaction with the anticancer drug danusertib nitrenium radical product using the DNA-electrochemical biosensor.

Danusertib is a kinase inhibitor and anti-cancer drug. The evaluation of the interaction between danusertib and dsDNA was investigated in bulk solution and using the dsDNA-electrochemical biosensor. The dsDNA-danusertib interaction occurs in two sequential steps.

Triazole-linked phenyl derivatives: redox mechanisms and in situ electrochemical evaluation of interaction with dsDNA.

The redox mechanism of two trisubstituted triazole-linked phenyl derivatives (CL41 and CL42) and a disubstituted triazole-linked phenyl derivative (CL2r50) were studied using cyclic, differential pulse and square wave voltammetry at a glassy carbon electrode. The CL41, CL42 and CL2r50 oxidation is a complex, pH-dependent irreversible process involving the formation of electroactive products that undergo two consecutive reversible oxidation reactions. The DNA interaction with CL41, CL42 and CL2r50 was investigated by differential pulse voltammetry using the dsDNA-electrochemical biosensor and in DNA/trisubstituted triazole incubated solutions.

Electrochemical evaluation of glutathione S-transferase kinetic parameters.

Glutathione S-transferases (GSTs), are a family of enzymes belonging to the phase II metabolism that catalyse the formation of thioether conjugates between the endogenous tripeptide glutathione and xenobiotic compounds. The voltammetric behaviour of glutathione (GSH), 1-chloro-2,4-dinitrobenzene (CDNB) and glutathione S-transferase (GST), as well as the catalytic conjugation reaction of GSH to CDNB by GST was investigated at room temperature, T=298.15K (25°C), at pH6.

In situ evaluation of gemcitabine-DNA interaction using a DNA-electrochemical biosensor.

The electrochemical behaviour of the cytosine nucleoside analogue and anti-cancer drug gemcitabine (GEM) was investigated at glassy carbon electrode, using cyclic, differential pulse and square wave voltammetry, in different pH supporting electrolytes, and no electrochemical redox process was observed. The evaluation of the interaction between GEM and DNA in incubated solutions and using the DNA-electrochemical biosensor was studied. The DNA structural modifications and damage were electrochemically detected following the changes in the oxidation peaks of guanosine and adenosine residues and the occurrence of the free guanine residues electrochemical signal.

Quadruplex nanostructures of d(TGGGGT): influence of sodium and potassium ions.

The Tetrahymena telomeric repeat sequence d(TG4T) contains only guanine (G) and thymine (T) bases and has medical and nanotechnological applications because of its ability to self-assemble into stiff tetra-molecular parallel-stranded G-quadruplexes. The hexadeoxynucleotide d(TG4T) was studied using atomic force microscopy (AFM) on the highly oriented pyrolytic graphite surface and differential pulse (DP) voltammetry at a glassy carbon electrode. The d(TG4T) single-strands self-assembled into G-quadruplex structures, very fast in K(+) ions solution and slowly in Na(+) ions containing solution.

Self-assembled G-quadruplex nanostructures: AFM and voltammetric characterization.

G-rich oligodeoxynucleotides (ODNs) have great medical and nanotechnological potential, because they can self-assemble into G-quadruplexes and higher-order nanostructures. The folding properties of d(G)10, d(TG9) and d(TG8T) ODNs were studied using atomic force microscopy (AFM) and voltammetry at carbon electrodes. Single-stranded ODNs, in Na(+) containing solutions and for short incubation times, were detected using AFM as network films and polymeric structures and using voltammetry by the occurrence of only the guanine oxidation peak.

Virgin olive oil ortho-phenols--electroanalytical quantification.

An electroanalytical methodology was developed for the determination of the total ortho-phenol content of virgin olive oil (VOO) with high sensitivity and reproducibility. The VOO ortho-phenol content depends on its freshness and is normally expressed as HT equivalent. Screen-printed electrodes were used with cyclic voltammetry to investigate the oxidation of catechol, phenol, hydroxytyrosol (HT), tyrosol, caffeic acid and ferulic acid.

In situ electrochemical evaluation of anticancer drug temozolomide and its metabolites-DNA interaction.

Temozolomide (TMZ) is an antineoplastic alkylating agent with activity against serious and aggressive types of brain tumours. It has been postulated that TMZ exerts its antitumor activity via its spontaneous degradation at physiological pH. The in vitro evaluation of the interaction of TMZ and its final metabolites, 5-aminoimidazole-4-carboxamide (AIC) and methyldiazonium ion, with double-stranded DNA (dsDNA) was studied using differential pulse voltammetry at a glassy carbon electrode.

Redox behaviour of verbascoside and rosmarinic acid.

The electrochemical oxidation mechanisms of rosmarinic acid (RA) and verbascoside (VB), both caffeic acid esters with two catechol moieties, were investigated. The redox mechanism is associated with the oxidation of the catechol groups, and was studied over a wide pH range by cyclic, differential pulse and square wave voltammetry, using a glassy carbon electrode. The voltammetric study revealed that both molecules, RA and VB, are reversibly oxidized in two successive pH-dependent steps each with the transfer of two electrons and two protons.