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Electrochemical oxidation of newly synthesized acridine derivatives (ADs): PG, PA, EG and EA was studied using square wave voltammetry at a glassy carbon electrode. Oxidation occurs as an irreversible process for all ADs. The ADs interaction with DNA was investigated using multi-layer DNA electrochemical biosensor. The shift of dA peak in positive direction indicated that the type of interaction is most likely an intercalation. PG showed the widest range of concentration capable to interact with DNA (1 × 10 -7 M - 2.5 × 10 -4 M). Analysing logI complex I DNA -I complex vslogc AD plots, the binding constants were determined. For the lowest PG concentrations, obtained K value close to 10 6 M -1 refers to strong binding. The values of K for PA may be classified as medium strength, while EG and EA showed low K values. Our results unequivocally showed that the characteristics of association complexes may vary depending on the concentration of the interacting substance. The negative ΔG value for all ADs, (- 21 to - 34 kJ mol -1 ), confirms the process spontaneity. The best result, indicating the most stable formed complex with DNA adsorbed at the electrode surface, showed PG when present in low concentration, order of 10 -7 M. The intercalation of ADs into DNA was supported by molecular docking analysis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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 -7 M (the lowest 9Cl-A concentration whose interaction with DNA was possible to detect) up to 1×10 -4 M. These allowed the binding constant, K=3.45×10 5 M -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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)