Pixantrone anticancer drug as a DNA ligand: Depicting the mechanism of action at single molecule level

Lima, Carlos Henrique Moreira; Caquito, J. M.; Oliveira, R. M. de; Rocha, M. S.

doi:10.1140/epje/i2019-11895-6

Cited by 6 publications

(1 citation statement)

References 38 publications

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“…As mentioned in the Results (refer to Section 2.2.3), the spring and viscosity constants of DNA, which were evaluated from the time-dependent conformational fluctuation in solution observed through FM, reflect the effect of the platinum compounds on the physical property of their higher-order structure in a sensitive manner. As for the measurement of the elastic property of DNA, a number of publications have appeared, during the past couple of decades, that report the use of laser tweezers through the chemical modification with the binding of a micrometer-sized plastic sphere at the end of the DNA molecule (e.g., [51][52][53]). Unfortunately, most of these studies have reported the observed spring constant for DNA molecules shorter than several kbp, which is attributable to the technical difficulty of the measurement on individual giant DNA molecules.…”

Section: Discussionmentioning

confidence: 99%

Different Effects of Cisplatin and Transplatin on the Higher-Order Structure of DNA and Gene Expression

Kishimoto

Yoshikawa

et al. 2019

IJMS

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Despite the effectiveness of cisplatin as an anticancer agent, its trans-isomer, transplatin, is clinically ineffective. Although both isomers target nuclear DNA, there is a large difference in the magnitude of their biological effects. Here, we compared their effects on gene expression in an in vitro luciferase assay and quantified their effects on the higher-order structure of DNA using fluorescence microscopy (FM) and atomic force microscopy (AFM). The inhibitory effect of cisplatin on gene expression was about 7 times that of transplatin. Analysis of the fluctuation autocorrelation function of the intrachain Brownian motion of individual DNA molecules showed that cisplatin increases the spring and damping constants of DNA by one order of magnitude and these visco-elastic characteristics tend to increase gradually over several hours. Transplatin had a weaker effect, which tended to decrease with time. These results agree with a stronger inhibitory effect of cisplatin on gene expression. We discussed the characteristic effects of the two compounds on the higher-order DNA structure and gene expression in terms of the differences in their binding to DNA.

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Section: Discussionmentioning

confidence: 99%

Different Effects of Cisplatin and Transplatin on the Higher-Order Structure of DNA and Gene Expression

Kishimoto

Yoshikawa

et al. 2019

IJMS

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Electrochemical Characteristics of a Novel Pyridinium Salt as a Candidate Drug Molecule and Its Interaction with DNA

et al. 2020

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In this article, for the first time, the electrochemical properties of a novel pyridine derivative, 4‐(2‐(2‐hydroxybenzylidene) hydrazinyl)‐1‐(3‐phenylpropyl) pyridinium bromide (abbreviated as 4‐Pyri), and its interaction with double stranded DNA (dsDNA) was investigated. The interaction between candidate drug molecule (4‐Pyri) and dsDNA was analyzed by examining 4‐Pyri (+0.6 V and +0.8 V) and guanine (+1.0 V) oxidation signal changes with Differential Pulse Voltammetry (DPV) and Cyclic Voltammetry (CV). Electrochemical Impedance Spectroscopy (EIS) was used to show the resistance changes before and after the interaction between 4‐Pyri and dsDNA. We showed that after the interaction with 4‐Pyri, the oxidation currents of guanine decreased dramatically, whereas the intrinsic oxidation currents of 4‐Pyri dramatically increased. 4‐Pyri oxidation current differences before and after the interaction with dsDNA enabled us to determine such interaction separately from guanine oxidation signals. In addition, resistance differences were observed at before and after the interaction with each other that confirmed the possible interaction. In addition, toxicity effect (S%) value, which is an important parameter for electrochemical studies indicated 4‐Pyri's toxicity to dsDNA. Our results demonstrated that 4‐Pyri interacts with dsDNA, and could be used as a potential candidate drug molecule due to its remarkable impact on dsDNA.

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Single molecule force spectroscopy of DNA-ligand complexes in the entropic regime

Rocha¹

2023

DNA Interactions With Drugs and Other Small Ligands

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Pixantrone anticancer drug as a DNA ligand: Depicting the mechanism of action at single molecule level

Cited by 6 publications

References 38 publications

Different Effects of Cisplatin and Transplatin on the Higher-Order Structure of DNA and Gene Expression

Different Effects of Cisplatin and Transplatin on the Higher-Order Structure of DNA and Gene Expression

Electrochemical Characteristics of a Novel Pyridinium Salt as a Candidate Drug Molecule and Its Interaction with DNA

Single molecule force spectroscopy of DNA-ligand complexes in the entropic regime

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