Electrochemical oxidation of the antitumor antibiotic mitomycin C and in situ evaluation of its interaction with DNA using a DNA-electrochemical biosensor

2017 ◽  
Vol 133 ◽  
pp. 81-89 ◽  
Author(s):  
Evellin Enny S. Bruzaca ◽  
Ilanna C. Lopes ◽  
Elizaura Hyeda C. Silva ◽  
Paulina Andréa V. Carvalho ◽  
Auro A. Tanaka
2014 ◽  
Vol 26 (6) ◽  
pp. 1304-1311 ◽  
Author(s):  
Inês B. Santarino ◽  
Severino Carlos B. Oliveira ◽  
Ana Maria Oliveira-Brett

1978 ◽  
Vol 56 (5) ◽  
pp. 296-304 ◽  
Author(s):  
J. William Lown ◽  
Gordon Weir

The reactions of the antitumor antibiotic mitomycin B with DNA were examined using ethidium fluorescence assays. The following three aspects of mitomycin B action have been studied to compare its behavior with that of mitomycin C: (a) interstrand cross-linking events, (b) alkylation without necessarily cross-linking, and (c) strand breakage. The greater pKa value of 4.3 found for mitomycin B compared with that of mitomycin C, i.e., 3.2, together with the greater pH dependence of DNA alkylation and interstrand cross-linking and the faster and more extensive cross-linking by mitomycin B at low pH in the absence of reduction, support the suggestion that the aziridine moiety is involved in the initial alkylation of DNA. Mitomycin B, reduced in situ with NaBH4, nicks covalenty closed circular (CCC) PM2 DNA rapidly but less efficiently than mitomycin C in a reaction which is suppressed by (i) superoxide dismutase, (ii) catalase, and (iii) free radical traps showing the intermediacy of O−2∙, H2O2, and OH∙. DNA is cleaved by mitomycin B to which it is covalently attached as well as by the free antibiotic. The addition of intercalated ethidium bromide to DNA prior to treatment with reduced mitomycin B inhibits interstrand cross-linking but not strand scission. The reduced aziridine ring-opened mitomycin B (which lacks the 7-NH2 group of mitomycin C) alkylates DNA and thus provides evidence confirming a previous suggestion that the second covalent link to the DNA is formed at position 10 of the antibiotic.


2021 ◽  
Vol 15 (1) ◽  
pp. 559-566
Author(s):  
Muhammad Tariq Riaz ◽  
Muhammad Yaqub ◽  
Shumaila Javed ◽  
Dilshad Hussain ◽  
Muhammad Naeem Ashiq ◽  
...  

2011 ◽  
Vol 13 (12) ◽  
pp. 5227 ◽  
Author(s):  
Ana Dora Rodrigues Pontinha ◽  
Sônia Maria Alves Jorge ◽  
Ana-Maria Chiorcea Paquim ◽  
Victor Constantin Diculescu ◽  
Ana Maria Oliveira-Brett

Sensors ◽  
2021 ◽  
Vol 21 (4) ◽  
pp. 1125 ◽  
Author(s):  
Ana-Maria Chiorcea-Paquim ◽  
Ana Maria Oliveira-Brett

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.


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