{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T10:57:15Z","timestamp":1762253835704,"version":"build-2065373602"},"reference-count":39,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T00:00:00Z","timestamp":1624492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006595","name":"Unitatea Executiva pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si Inovarii","doi-asserted-by":"publisher","award":["58PCCDI"],"award-info":[{"award-number":["58PCCDI"]}],"id":[{"id":"10.13039\/501100006595","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Programul Operational de Competivitate","award":["NANOBIOSURF-SMIS 103258"],"award-info":[{"award-number":["NANOBIOSURF-SMIS 103258"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The electrochemical behavior and the interaction of the immunosuppressive drug azathioprine (AZA) with deoxyribonucleic acid (DNA) were investigated using voltammetric techniques, mass spectrometry (MS), and scanning electron microscopy (SEM). The redox mechanism of AZA on glassy carbon (GC) was investigated using cyclic and differential pulse (DP) voltammetry. It was proven that the electroactive center of AZA is the nitro group and its reduction mechanism is a diffusion-controlled process, which occurs in consecutive steps with formation of electroactive products and involves the transfer of electrons and protons. A redox mechanism was proposed and the interaction of AZA with DNA was also investigated. Morphological characterization of the DNA film on the electrode surface before and after interaction with AZA was performed using scanning electron microscopy. An electrochemical DNA biosensor was employed to study the interactions between AZA and DNA with different concentrations, incubation times, and applied potential values. It was shown that the reduction of AZA molecules bound to the DNA layer induces structural changes of the DNA double strands and oxidative damage, which were recognized through the occurrence of the 8-oxo-deoxyguanosine oxidation peak. Mass spectrometry investigation of the DNA film before and after interaction with AZA also demonstrated the formation of AZA adducts with purine bases.<\/jats:p>","DOI":"10.3390\/ijms22136805","type":"journal-article","created":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T11:01:38Z","timestamp":1624532498000},"page":"6805","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Redox Mechanism of Azathioprine and Its Interaction with DNA"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8014-528X","authenticated-orcid":false,"given":"Mihaela-Cristina","family":"Bunea","sequence":"first","affiliation":[{"name":"Laboratory of Multifunctional Materials and Structures, National Institute of Materials Physics, Atomistilor 405A, 077125 Magurele, Romania"},{"name":"Advanced Polymer Materials Group, University Politehnica of Bucharest, 1-7 Gh. Polizu, 011061 Bucharest, Romania"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0719-8016","authenticated-orcid":false,"given":"Victor-Constantin","family":"Diculescu","sequence":"additional","affiliation":[{"name":"Laboratory of Multifunctional Materials and Structures, National Institute of Materials Physics, Atomistilor 405A, 077125 Magurele, Romania"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4476-5545","authenticated-orcid":false,"given":"Monica","family":"Enculescu","sequence":"additional","affiliation":[{"name":"Laboratory of Multifunctional Materials and Structures, National Institute of Materials Physics, Atomistilor 405A, 077125 Magurele, Romania"}]},{"given":"Horia","family":"Iovu","sequence":"additional","affiliation":[{"name":"Advanced Polymer Materials Group, University Politehnica of Bucharest, 1-7 Gh. Polizu, 011061 Bucharest, Romania"}]},{"given":"Teodor Adrian","family":"Enache","sequence":"additional","affiliation":[{"name":"Laboratory of Multifunctional Materials and Structures, National Institute of Materials Physics, Atomistilor 405A, 077125 Magurele, Romania"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1111\/j.1751-1097.1986.tb05601.x","article-title":"Photochemical sensitization by azathioprine and its metabolites-i. 6-mercaptopurine","volume":"43","author":"Hemmens","year":"1986","journal-title":"Photochem. Photobiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6404","DOI":"10.1021\/ja010378c","article-title":"Mechanism of activation of an immunosuppressive drug: Azathioprine. Quantum chemical study on the reaction of aza-thioprine with cysteine","volume":"123","author":"Hoffmann","year":"2001","journal-title":"J. Am. Chem. Soc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1172\/JCI200318384","article-title":"Azathioprine: Old drug, new actions","volume":"111","author":"Maltzman","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_4","first-page":"1","article-title":"Azathioprine for multiple sclerosis","volume":"4","author":"Casetta","year":"2007","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"121802","DOI":"10.1016\/j.jchromb.2019.121802","article-title":"Highly sensitive and rapid determination of azathioprine metabolites in whole blood lysate by liquid chroma-tography\u2013tandem mass spectrometry","volume":"1136","author":"Miao","year":"2020","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/0731-7085(87)80053-5","article-title":"Principles and practice of drug photodegradation studies","volume":"5","author":"Moore","year":"1987","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1111\/j.1365-2133.2008.08610.x","article-title":"Azathioprine treatment photosensitizes human skin to ultraviolet A radiation","volume":"159","author":"Perrett","year":"2008","journal-title":"Br. J. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1111\/j.1751-1097.1986.tb05602.x","article-title":"Photochemical Sensitization By Azathioprine and Its Metabo-lites\u2014Ii. Azathioprine and Nitroimidazole Metabolites","volume":"43","author":"Hemmens","year":"1986","journal-title":"Photochem. Photobiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.cej.2016.05.085","article-title":"Kinetic and mechanistic investigation of azathioprine degradation in water by UV, UV\/H 2 O 2 and UV\/persulfate","volume":"302","author":"Zhang","year":"2016","journal-title":"Chem. Eng. J."},{"key":"ref_10","first-page":"261","article-title":"Azathioprine, UV light, and skin cancer in organ transplant patients do we have an answer?","volume":"23","author":"Ulrich","year":"2000","journal-title":"Med. Monatsschr. Pharm."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.ijbiomac.2015.08.025","article-title":"Electrochemical, spectroscopic, and theoretical studies on the interaction between azathioprine and DNA","volume":"81","author":"Jalali","year":"2015","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1134\/S1023193515010097","article-title":"Voltammetric determination of immunosuppressive agent, azathioprine, by using a graphene-chitosan modified-glassy carbon electrode","volume":"51","author":"Hatami","year":"2015","journal-title":"Russ. J. Electrochem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1016\/j.elecom.2009.05.025","article-title":"Electrochemical study of Azathioprine at thin carbon nano-particle composite film electrode","volume":"11","author":"Shahrokhian","year":"2009","journal-title":"Electrochem. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3621","DOI":"10.1016\/j.electacta.2010.01.099","article-title":"Glassy carbon electrodes modified with a film of nanodia-mond-graphite\/chitosan: Application to the highly sensitive electrochemical determination of Azathioprine","volume":"55","author":"Shahrokhian","year":"2010","journal-title":"Electrochim. Acta"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.colsurfa.2018.09.047","article-title":"In-situ decorated silver nanoparticles on elec-trospun poly (vinyl alcohol)\/chitosan nanofibers as a plasmonic sensor for azathioprine deter-mination, Colloids Surfaces A Physicochem","volume":"559","author":"Rastegarzadeh","year":"2018","journal-title":"Eng. Asp."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.snb.2015.03.014","article-title":"Green electrodeposition of gold hierarchical dendrites of pyramidal nanoparticles and determination of azathioprine","volume":"215","author":"Vais","year":"2015","journal-title":"Sens. Actuators B Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.jelechem.2016.05.022","article-title":"Advances in electrochemical DNA biosensors and their interaction mechanism with pharma-ceuticals","volume":"775","author":"Kurbanoglu","year":"2016","journal-title":"J. Electroanal. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.bioelechem.2011.07.004","article-title":"Nucleoside analogue electrochemical behaviour and in situ evaluation of DNA\u2013clofarabine interaction","volume":"87","author":"Satana","year":"2012","journal-title":"Bioelectrochemistry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/S0039-9140(01)00656-7","article-title":"Electrochemical detection of in situ adriamycin oxidative damage to DNA","volume":"56","author":"Vivan","year":"2002","journal-title":"Talanta"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5227","DOI":"10.1039\/c0cp02377a","article-title":"In situ evaluation of anticancer drug methotrexate\u2013DNA interaction using a DNA-electrochemical biosensor and AFM characterization","volume":"13","author":"Pontinha","year":"2011","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.bioelechem.2014.05.005","article-title":"In situ evaluation of gemcitabine\u2013DNA interaction using a DNA-electrochemical biosensor","volume":"99","author":"Buoro","year":"2014","journal-title":"Bioelectrochemistry"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.jpba.2004.10.037","article-title":"Electrochemical approach of anticancer drugs\u2013DNA interaction","volume":"37","author":"Rauf","year":"2005","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/j.talanta.2017.08.089","article-title":"Electrochemical monitoring of the interaction between anticancer drug and DNA in the presence of antioxidant","volume":"178","author":"Muti","year":"2018","journal-title":"Talanta"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1002\/elan.201100516","article-title":"DNA-Cyanobacterial Hepa-totoxins Microcystin-LR and Nodularin Interaction: Electrochemical Evaluation","volume":"24","author":"Santos","year":"2012","journal-title":"Electroanalysis"},{"key":"ref_25","first-page":"413","article-title":"Chapter 20 DNA-electrochemical biosensors for investigating DNA damage","volume":"49","author":"Brett","year":"2007","journal-title":"Compr. Anal. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.jphotobiol.2014.05.015","article-title":"In vitro DNA binding studies of anticancer drug idarubicin using spectroscopic techniques","volume":"138","author":"Ozluer","year":"2014","journal-title":"J. Photochem. Photobiol. B Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.bioelechem.2004.05.002","article-title":"Electrochemical study of quercetin-DNA interactions: Part II. In situ sensing with DNA biosensors","volume":"64","author":"Diculescu","year":"2004","journal-title":"Bioelectrochemistry"},{"key":"ref_28","first-page":"1","article-title":"Electrochemical DNA Biosensors in Drug Analysis","volume":"12","author":"Karadurmus","year":"2017","journal-title":"Curr. Pharm. Anal."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.aca.2006.03.085","article-title":"Deoxyribonucleic acid (DNA) biosensors for en-vironmental risk assessment and drug studies","volume":"573\u2013574","author":"Bagni","year":"2006","journal-title":"Anal. Chim. Acta"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3122","DOI":"10.3390\/s90403122","article-title":"Overview of Electrochemical DNA Biosensors: New Approaches to Detect the Expression of Life","volume":"9","author":"Cagnin","year":"2009","journal-title":"Sensors"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.trac.2016.01.019","article-title":"Applications of a DNA-electrochemical biosensor","volume":"79","author":"Diculescu","year":"2016","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.aca.2020.07.071","article-title":"De-velopment of a new electrochemical DNA biosensor based on Eu3+\u2212doped NiO for determi-nation of amsacrine as an anti-cancer drug: Electrochemical, spectroscopic and docking stud-ies","volume":"1133","author":"Dehghannoudeh","year":"2020","journal-title":"Anal. Chim. Acta."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3251","DOI":"10.1007\/s10008-014-2664-z","article-title":"Planar diffusion to macro disc elec-trodes\u2014what electrode size is required for the Cottrell and Randles-Sevcik equations to apply quantitatively?","volume":"18","author":"Ngamchuea","year":"2014","journal-title":"J. Solid State Electrochem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1002\/aic.690010222","article-title":"Correlation of diffusion coefficients in dilute solutions","volume":"1","author":"Wilke","year":"1955","journal-title":"AIChE J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6639","DOI":"10.1016\/j.chroma.2011.07.018","article-title":"Estimation of molecular diffusivity in liquid phase systems by the Wilke\u2013Chang equation","volume":"1218","author":"Miyabe","year":"2011","journal-title":"J. Chromatogr. A"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.bioelechem.2006.03.015","article-title":"Electrochemical behaviour of 2,8-dihydroxyadenine at a glassy carbon electrode","volume":"70","author":"Diculescu","year":"2007","journal-title":"Bioelectrochemistry"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1002\/1521-4109(200008)12:12<969::AID-ELAN969>3.0.CO;2-O","article-title":"Electrochemical Oxidation of 8-Oxoguanine","volume":"12","author":"Brett","year":"2000","journal-title":"Electroanalysis"},{"key":"ref_38","first-page":"177","article-title":"DNA adducts and carcinogenicity of nitro-polycyclic aromatic hydrocarbons","volume":"102","author":"Fu","year":"1994","journal-title":"Environ. Health Perspect."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1021\/tx010172p","article-title":"DNA Adducts from Nitroreduction of 2,7-Dinitrofluorene, a Mammary Gland Carcinogen, Catalyzed by Rat Liver or Mammary Gland Cytosol","volume":"15","author":"Ritter","year":"2002","journal-title":"Chem. Res. Toxicol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/13\/6805\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:23:12Z","timestamp":1760163792000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/13\/6805"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,24]]},"references-count":39,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["ijms22136805"],"URL":"https:\/\/doi.org\/10.3390\/ijms22136805","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2021,6,24]]}}}