Thomaz Douglas Vieira, de Oliveira Matheus Gabriel, Rodrigues Edson Silvio Batista, da Silva Vinicius Barreto, Dos Santos Pierre Alexandre
Faculty of Pharmacy, Federal University of Goias, Goiania-GO 74605-170, Brazil.
Department of Pharmacy, Pontifical Catholic University of Goias, Goiania-GO 74175-120, Brazil.
Pharmaceuticals (Basel). 2020 May 28;13(6):108. doi: 10.3390/ph13060108.
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 () ≈ 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 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.
这项工作展示了通过电分析方法对补骨脂素（PSO）与双链DNA（dsDNA）结合进行的首次物理化学研究。结果表明，PSO在电势（）≈1.42 V处呈现一个不可逆的阳极峰，这与其氧化及环氧化物衍生物的形成有关。此外，随着dsDNA的加入，PSO的分析信号（即法拉第电流）呈线性下降，而与PSO氧化相关的电势向更正的值移动，由此表明加入dsDNA会阻碍PSO氧化。化学信息学研究证实了这些发现，该研究表明PSO首先非共价地插入DNA双链的碱基对之间，然后与两条DNA链不可逆地形成加合物，导致形成一条连接DNA螺旋的交联键，这解释了PSO氧化产生的法拉第电流与测试溶液中DNA浓度之间的线性关系，以及与dsDNA溶液加入量之间的关系。因此，本文报道的研究结果证明了电分析方法，如伏安法在DNA嵌入剂研究中的适用性。
