An electrochemical study of 9-chloroacridine redox behavior and its interaction with double-stranded DNA
Abstract
The electrochemical behavior of 9-chloroacridine (9Cl-A), a precursor molecule for synthesis of acridine derivatives with cytostatic activity, is a complex, pH-dependent, diffusion-controlled irreversible process. Oxidation of 9Cl-A initiates with the formation of a cation radical monomer, continues via the formation of a dimer subsequent oxidation to new cation radical. Reduction of 9Cl-A produces radical monomers which are stabilized by dimer formation. The investigation was performed using cyclic, differential pulse and square wave voltammetry at a glassy carbon electrode. The interaction between 9Cl-A and double-stranded DNA (dsDNA) was investigated using a multilayer dsDNA-electrochemical biosensor and 9Cl-A solutions from 1.0×10-7M (the lowest 9Cl-A concentration whose interaction with DNA was possible to detect) up to 1×10-4M. These allowed the binding constant, K=3.45×105M-1 and change in Gibbs free energy of the formed adsorbed complex to be calculated. Complex formation was a... spontaneous process proceeding via 9Cl-A intercalation into dsDNA inducing structural changes. The intercalation of 9Cl-A into dsDNA was supported by molecular docking analysis. The combination of simple methodology and the use of biosensors to investigate DNA interactions is a powerful tool to offer insight into aspects of drug design during pharmaceutical development.
Keywords:
9-Chloroacridine redox mechanism / dsDNA-electrochemical biosensor / Interaction / Molecular docking / Square wave voltammetrySource:
Bioelectrochemistry, 2020, 135Publisher:
- Elsevier B.V.
Funding / projects:
- Synthesis, Quantitative Structure and Activity Relationship, Physico-Chemical Characterisation and Analysis of Pharmacologically Active Substances (RS-172033)
- Development of molecules with antiinflammatory and cardioprotective activity: structural modifications, modelling, physicochemical characterization and formulation investigations (RS-172041)
DOI: 10.1016/j.bioelechem.2020.107579
ISSN: 1567-5394
WoS: 000579730600005
Scopus: 2-s2.0-85086144465
Collections
Institution/Community
PharmacyTY - JOUR AU - Rupar, Jelena AU - Aleksić, Mara AU - Dobričić, Vladimir AU - Brborić, Jasmina AU - Čudina, Olivera PY - 2020 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3611 AB - The electrochemical behavior of 9-chloroacridine (9Cl-A), a precursor molecule for synthesis of acridine derivatives with cytostatic activity, is a complex, pH-dependent, diffusion-controlled irreversible process. Oxidation of 9Cl-A initiates with the formation of a cation radical monomer, continues via the formation of a dimer subsequent oxidation to new cation radical. Reduction of 9Cl-A produces radical monomers which are stabilized by dimer formation. The investigation was performed using cyclic, differential pulse and square wave voltammetry at a glassy carbon electrode. The interaction between 9Cl-A and double-stranded DNA (dsDNA) was investigated using a multilayer dsDNA-electrochemical biosensor and 9Cl-A solutions from 1.0×10-7M (the lowest 9Cl-A concentration whose interaction with DNA was possible to detect) up to 1×10-4M. These allowed the binding constant, K=3.45×105M-1 and change in Gibbs free energy of the formed adsorbed complex to be calculated. Complex formation was a spontaneous process proceeding via 9Cl-A intercalation into dsDNA inducing structural changes. The intercalation of 9Cl-A into dsDNA was supported by molecular docking analysis. The combination of simple methodology and the use of biosensors to investigate DNA interactions is a powerful tool to offer insight into aspects of drug design during pharmaceutical development. PB - Elsevier B.V. T2 - Bioelectrochemistry T1 - An electrochemical study of 9-chloroacridine redox behavior and its interaction with double-stranded DNA VL - 135 DO - 10.1016/j.bioelechem.2020.107579 ER -
@article{ author = "Rupar, Jelena and Aleksić, Mara and Dobričić, Vladimir and Brborić, Jasmina and Čudina, Olivera", year = "2020", abstract = "The electrochemical behavior of 9-chloroacridine (9Cl-A), a precursor molecule for synthesis of acridine derivatives with cytostatic activity, is a complex, pH-dependent, diffusion-controlled irreversible process. Oxidation of 9Cl-A initiates with the formation of a cation radical monomer, continues via the formation of a dimer subsequent oxidation to new cation radical. Reduction of 9Cl-A produces radical monomers which are stabilized by dimer formation. The investigation was performed using cyclic, differential pulse and square wave voltammetry at a glassy carbon electrode. The interaction between 9Cl-A and double-stranded DNA (dsDNA) was investigated using a multilayer dsDNA-electrochemical biosensor and 9Cl-A solutions from 1.0×10-7M (the lowest 9Cl-A concentration whose interaction with DNA was possible to detect) up to 1×10-4M. These allowed the binding constant, K=3.45×105M-1 and change in Gibbs free energy of the formed adsorbed complex to be calculated. Complex formation was a spontaneous process proceeding via 9Cl-A intercalation into dsDNA inducing structural changes. The intercalation of 9Cl-A into dsDNA was supported by molecular docking analysis. The combination of simple methodology and the use of biosensors to investigate DNA interactions is a powerful tool to offer insight into aspects of drug design during pharmaceutical development.", publisher = "Elsevier B.V.", journal = "Bioelectrochemistry", title = "An electrochemical study of 9-chloroacridine redox behavior and its interaction with double-stranded DNA", volume = "135", doi = "10.1016/j.bioelechem.2020.107579" }
Rupar, J., Aleksić, M., Dobričić, V., Brborić, J.,& Čudina, O.. (2020). An electrochemical study of 9-chloroacridine redox behavior and its interaction with double-stranded DNA. in Bioelectrochemistry Elsevier B.V.., 135. https://doi.org/10.1016/j.bioelechem.2020.107579
Rupar J, Aleksić M, Dobričić V, Brborić J, Čudina O. An electrochemical study of 9-chloroacridine redox behavior and its interaction with double-stranded DNA. in Bioelectrochemistry. 2020;135. doi:10.1016/j.bioelechem.2020.107579 .
Rupar, Jelena, Aleksić, Mara, Dobričić, Vladimir, Brborić, Jasmina, Čudina, Olivera, "An electrochemical study of 9-chloroacridine redox behavior and its interaction with double-stranded DNA" in Bioelectrochemistry, 135 (2020), https://doi.org/10.1016/j.bioelechem.2020.107579 . .