In the present study, the electrochemical behavior of antiviral drug umifenovir (Umi) and umifenovir encapsulated in phospholipids micelles (nanosome/umifenovir, NUmi) were investigated for the first time on screen-printed electrodes modified by carbon nanotubes. We have shown that Umi can be electro oxidized around the potential of +0.4 V in the concentration range of 50–500 µM (R2 = 0.992). Non-overlapping signatures of DNA and umifenovir (10–150 µM) permit to register interaction between umifenovir (or umifenovir encapsulated in phospholipids micelles), purine, and pyrimidine heterocyclic bases of DNA separately. The type of interaction is most likely via electrostatic interactions and groove binding in drug-DNA formed complex, as was revealed based on the values of binding constants Kb and the cathodic shifts of oxidation potentials for heterocyclic bases with increasing Umi or NUmi concentration. The negative values of Gibbs free energy (ΔG) for all nucleobases confirm the process spontaneity. This study is the first one presenting the effect of antiviral drug umifenovir and umifenovir encapsulated in phospholipids micelles on dsDNA as a target of pharmacogenomics.

The effect of phospholipid nanoparticles with different contents of phosphatidylcholine (PhNP80 and PhNP100) on dsDNA was studied by means of the electrochemical method. Changes in the electrochemical behavior of heterocyclic bases guanine, adenine and thymine in the range of potentials of 0.2–1.2 V in the presence of PhNPs were used for the assessment of the binding mechanism of the ligand–DNA interaction. Comparative analysis of the effect of PhNPs with different contents of phosphatidylcholine showed a more pronounced effect on the dsDNA of the PhNP100 nanosystem. From the obtained experimental data on the decrease in the amplitude of the nucleobases' electrochemical oxidation currents, the electrochemical coefficient of the toxic effect was calculated as the ratio of the electrooxidation currents of dsDNA and dsDNA in the presence of phospholipid nanoparticles. PhNP80/100 (up to 11.4 mg/mL) does not influence dsDNA, PhNP80/100 (14.3–28.5 mg/mL) has a moderate toxic effect on dsDNA, PhNP80/100 at concentrations above 28.5 mg/mL already have a toxic effect, significantly reducing the maximum amplitude of the heterocyclic bases’ electrochemical oxidation current. Peak potentials of electrochemical oxidation of nucleobases did not shift in the presence of PhNP80 and PhNP100 (in the concentration range of 2.3–42.2 mg/mL), which could be possible through a groove-binding mode of phospholipid nanoparticle interaction with dsDNA.

The functional significance of cytochrome P450s (CYP) enzymes is their ability to catalyze the biotransformation of xenobiotics and endogenous compounds. P450 enzymes catalyze regio- and stereoselective oxidations of C-C and C-H bonds in the presence of oxygen as a cosubstrate. Initiation of cytochrome P450 catalytic cycle needs an electron donor (NADPH, NADH cofactor) in nature or alternative artificial electron donors such as electrodes, peroxides, photo reduction, and construction of enzymatic “galvanic couple”. In our review paper, we described alternative “handmade” electron sources to support cytochrome P450 catalysis. Physical-chemical methods in relation to biomolecules are possible to convert from laboratory to industry and construct P450-bioreactors for practical application. We analyzed electrochemical reactions using modified electrodes as electron donors. Electrode/P450 systems are the most analyzed in terms of the mechanisms underlying P450-catalyzed reactions. Comparative analysis of flat 2D and nanopore 3D electrode modifiers is discussed. Solar-powered photobiocatalysis for CYP systems with photocurrents providing electrons to heme iron of CYP and photoelectrochemical biosensors are also promising alternative light-driven systems. Several examples of artificial “galvanic element” construction using Zn as an electron source for the reduction of Fe3+ ion of heme demonstrated potential application. The characteristics, performance, and potential applications of P450 electrochemical systems are also discussed.

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