Abstract

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. The DNA electrochemical biosensor development, from the viewpoint of electrochemical and atomic force microscopy (AFM) characterization, and the bottom-up immobilization of DNA nanostructures at the electrode surface, are described. Applications of DNA electrochemical biosensors that enable the label-free detection of DNA interactions with pharmaceutical compounds, such as acridine derivatives, alkaloids, alkylating agents, alkylphosphocholines, antibiotics, antimetabolites, kinase inhibitors, immunomodulatory agents, metal complexes, nucleoside analogs, and phenolic compounds, which can be used in drug analysis and drug discovery, and may lead to future screening systems, are reviewed.

Highlights

  • Deoxyribonucleic acid (DNA) is the most important element of the genetic apparatus, playing a dual role, carrying genetic information and regulating its expression

  • Antimetabolites are a large group of anticancer agents that structurally resemble substrates naturally produced by the body, but are different enough to interfere with their metabolism

  • The rituximab–dsDNA interaction was studied in incubated solutions and with a multilayer dsDNA electrochemical biosensor [100], demonstrating that rituximab induces the condensation of the DNA double helix, identified by the decrease and disappearance of the A residue (Ar) oxidation peak current, the

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Summary

Introduction

Deoxyribonucleic acid (DNA) is the most important element of the genetic apparatus, playing a dual role, carrying genetic information and regulating its expression. An and electrochemical nucleic acid-based biosensor is defined by the International damage cellular oxidative stress. The label-free DNA electrochemical biosensor sensing is based on the direct detection of the oxidation peaks of the DNA constituents, nucleotides, nucleosides, and purine and pyrimidine bases, and of the oxidation peaks of 8-oxoG and 2,8-DHA biomarkers of the oxidative DNA damage. This review presents the design, development, and applications of label-free DNA electrochemical biosensors based on direct DNA electrochemical detection, to assess the oxidative DNA damage caused by pharmaceutical compounds, relevant for drug discovery and analysis. The electrochemical and atomic force microscopy (AFM) characterization of different bottom-up immobilization strategies of DNA nanostructured films onto electrodes are described, and the biosensors’ applications for a wide range of pharmaceutical compounds, ranging from antibiotics and anticancer drugs to antibodies, are reviewed. This review is of great interest to the chemistry, biochemistry, and medical communities, because the 8-oxoG and 2,8-DHA biomarkers of oxidative DNA damage and cellular oxidative stress represent important parameters in the context of the development of innovative actions and systems that enable disease prevention, early diagnosis, and treatment in healthcare

Electrochemical Characterization
Electrochemical Detection of DNA Oxidation
Morphological
A DNA electrochemical biosensor built with thick multilayer
In theincubation presence of
DNA Electrochemical Biosensors for the Detection of Pharmaceutical Drugs
Acridine Derivatives
Alkaloids
Alkylating Agents
Alkylphosphocholines
Antibiotics
Antimetabolites
Kinaseimatinib
Immunomodulatory Agents
Nucleoside Analogs
3.10. Metal Complexes
3.11. Phenolic Compounds
Conclusions

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