Physicochemical investigation of Psoralen binding to double stranded DNA through electroanalytical and cheminformatic approaches

Vinicius Silva,Douglas Thomaz,Pierre Santos,Matheus Oliveira,Edson Rodrigues

doi:10.3390/ecmc2019-06298

Abstract

This work showcased the first physicochemical investigation of Psoralen (PSO) binding to double stranded DNA (dsDNA) through electroanalytical methods, whose results were further explored through a cheminformatic study. Results evidenced that PSO presents one non-reversible anodic peak at Epa ≈ 1.42 V which is associated with its oxidation and the formation of an epoxide derivative, moreover, PSO analytical signal (i.e. faradaic current) decreases linearly with the addition of dsDNA while the electric potential associated to PSO oxidation shifts towards more positive values, indicating therefore that dsDNA addition hinders PSO oxidation. These findings were corroborated by the chemoinformatic study, which evidenced that PSO intercalates noncovalently between base-pairs of the DNA duplex, and then irreversibly form adducts with both DNA strands, leading up to the formation of a cross-link which bridges DNA helix, what explains the linear dependence between the faradaic current generated by PSO oxidation and the concentration of dsDNA in the test-solution, as well as the dependence between Ep and the addition of dsDNA solution. Therefore, the findings herein reported evidence the applicability of electroanalytical approaches such as voltammetry in the study of DNA intercalating agents.

Highlights

Graphical AbstractAbstract: This work showcased the first physicochemical investigation of Psoralen (PSO) binding to double stranded DNA (dsDNA) through electroanalytical methods
Psoralen (PSO) is a photosensitizing linear furanocoumarin derivative (Figure 1) whose biologic potential is therapeutically explored to treat cutaneous conditions such as psoriasis and vitiligo, as well as some forms of cancer;
Results evidenced that PSO presents one non-reversible anodic peak at Epa ≈ 1.42 V which is associated with its oxidation and the formation of an epoxide derivative, PSO analytical signal decreases linearly with the addition of double stranded DNA (dsDNA) while the electric potential associated to PSO oxidation shifts towards more positive values, indicating thence that dsDNA addition hinders PSO oxidation

Summary

Graphical Abstract

Abstract: This work showcased the first physicochemical investigation of Psoralen (PSO) binding to double stranded DNA (dsDNA) through electroanalytical methods. Results evidenced that PSO presents one non-reversible anodic peak at Epa ≈ 1.42 V which is associated with its oxidation and the formation of an epoxide derivative, PSO analytical signal (i.e. faradaic current) decreases linearly with the addition of dsDNA while the electric potential associated to PSO oxidation shifts towards more positive values, indicating thence that dsDNA addition hinders PSO oxidation These findings were corroborated by the chemoinformatic study, which evidenced that PSO intercalates noncovalently between base-pairs of the DNA duplex, and irreversibly form adducts with both DNA strands, leading up to the formation of a cross-link which bridges DNA helix, what explains the linear dependence between the faradaic current generated by PSO oxidation and the concentration of DNA in the test-solution, as well as the dependence between Ep and the addition of dsDNA solution.

Introduction

Conclusions