Physicochemical Investigation of Psoralen Binding to Double Stranded DNA through Electroanalytical and Cheminformatic Approaches.

Douglas Vieira Thomaz,Vinicius Barreto Da Silva,Pierre Alexandre Dos Santos,Matheus Gabriel De Oliveira,Edson Silvio Batista Rodrigues

doi:10.3390/ph13060108

Douglas Vieira Thomaz, Vinicius Barreto Da Silva + Show 3 more

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https://doi.org/10.3390/ph13060108

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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 electric potential (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 thence that dsDNA addition hinders PSO oxidation. These findings were corroborated by the chemoinformatic study, which evidenced that PSO intercalated noncovalently at first between base-pairs of the DNA duplex, and then irreversibly formed adducts with both DNA strands, leading up to the formation of a cross-link which bridges the DNA helix, which 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. Therefore, the findings herein reported evidence of the applicability of electroanalytical approaches, such as voltammetry in the study of DNA intercalating agents.

Highlights

Psoralen (PSO) is a photosensitizing linear furanocoumarin derivative, whose biologic potential was therapeutically explored to treat cutaneous conditions such as psoriasis and vitiligo, as well as some forms of cancer [1,2,3,4,5]
PSO–double stranded DNA (dsDNA) binding is well reported in literature, and its kinetics and thermodynamics were thoroughly studied under spectrophotometric approaches, as the decrease of PSO absorbance values were a common finding [11]
1.5 g of calf-thymus dsDNA was diluted in 2 mL phosphate buffered saline (PBS), pH 7.0, in order to render a concentrated mixture for the studies

Summary

Introduction

Psoralen (PSO) is a photosensitizing linear furanocoumarin derivative, whose biologic potential was therapeutically explored to treat cutaneous conditions such as psoriasis and vitiligo, as well as some forms of cancer [1,2,3,4,5]. This compound is a secondary metabolite of several plant families (e.g., Fabaceae, Moraceae, Rutaceae, etc.), and its chemical structure is the building block of all linear furanocoumarin derivatives, whose healthcare uses can be either allopathic or folk medicine-based [6,7,8]. Furanocoumarin chemical structures are relatable to several small ligands, which may confer such a wide range of possible biological targets (Figure 1).

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