Comparative Analysis of the Interaction between the Antiviral Drug Umifenovir and Umifenovir Encapsulated in Phospholipids Micelles (Nanosome/Umifenovir) with dsDNA as a Model for Pharmacogenomic Analysis by Electrochemical Methods

Abstract

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.

Pharmacogenomic Studies of Antiviral Drug Favipiravir

“…Earlier, we showed that electrochemical oxidation of dsDNA was successfully achieved on SPE/CNT after dsDNA immobilization by physical entrapment/absorption on the surface of the modified electrodes. Modification of SPEswith CNT stabilized with carboxymethylcellulose (SPE/CNT) allowed the registering of electrochemical oxidation of guanine, adenine and thymine in the immobilized dsDNA [ 40 , 41 , 71 ]. Adding nanosized titanium (IV) oxide TiO 2 improved the sensitivity of electrodes for the registration of dsDNA ( Figure 4 a,b), as in the case of protein registration [ 43 ].…”

“…Based on this observation, we used SPEs only for single measurements. This regimen is typical for the irreversible electrochemical process [ 40 , 41 , 73 ].…”

“…The influence of FAV was also represented as the DNA-mediated electrochemical coefficient of toxicity using Equation (2): S = (Ss/Sb) × 100% where Sb and Ss are nucleobase oxidation signals before and after interaction of the FAV with dsDNA, respectively [ 40 , 41 , 84 ]. We used this criterion such that if a drug does not have a toxic effect, S is higher than 85%; it has a moderate toxic effect if the S parameter is between 50 and 85%, and has a toxic effect if S is below 50% [ 83 ].…”

“…Linear plots for 1/(I 0 − I) depending on 1/[FAV] were used for the calculation of the binding constant Kb [ 40 , 41 ] in accordance with the following equation: Kb ≈ (I 0 − I)/(I 0 × ([FAV] − (I 0 − I)).…”

Interaction of Doxorubicin Embedded into Phospholipid Nanoparticles and Targeted Peptide-Modified Phospholipid Nanoparticles with DNA

“…The aim of this study is to discover the effects of DOX, or DOX as nanoformulated forms (DOX-loaded NPhs and DOX with the NGR targeted peptide), onto DNA as a model molecule in pharmacogenomics. To assess the mechanism of interaction of medications with DNA, we used electrochemical techniques, which possess high sensitivity, selectivity, and registration of a concentration-dependent “response” of heterocyclic nucleobases on drug influence [ 12 , 21 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ].…”