Elucidation of binding interactions and mechanism of Fludarabine with dsDNA via multispectroscopic and molecular docking studies

Şenel, Pelin; Agar, Soykan; Sayin, V. Oyku; Altay, Filiz; Yurtsever, Mine; Gölcü, Ayşegül

doi:10.1016/j.jpba.2019.112994

Cited by 18 publications

(8 citation statements)

References 27 publications

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“…Based on our previous studies and scientific literature reports, the ultraviolet absorption titration technique is one of the most common and valid methods used to investigate DNA interactions. , The structural changes of DNA in the presence of any small compound, along with the affinity and binding mode of small molecules, are effectively seen from the UV electronic absorption spectrum. The absorption of DNA occurs due to the chromophoric groups (conjugated double bonds) of the pyrimidine and purine ring system within the structure.…”

Section: Results and Discussionmentioning

confidence: 86%

“…The decrease in the absorbance values and the absence of significant wavelength shifts in the experiments at the constant concentrations of APG (or ADSAM or ATSAM) showed that these compounds were binding to dsDNA via the groove-binding mode. In some important research studies, the same binding mode has been proposed in a significant number of compounds, for instance; anticancer drugs 6-thioguanine and fludarabine , with similar spectral properties, i.e., hypochromic in the presence of dsDNA and no shift in the wavelength. In addition, the DNA equilibrium binding constants ( K b ) of three compounds were calculated based on titration data.…”

Section: Results and Discussionmentioning

confidence: 86%

“…The change in viscosity upon molecular intercalation with dsDNA requires the condition that the distance of the adjacent base pairs should be large enough to be able to bind the small molecules (ligand or drug) within the double-stranded chain. The electrostatic or groove surface binders tend to make quite negligible and mostly no change in viscosity . Contrary to that, the increase of the viscosity of the nucleic acid solution indicates the intercalation mechanism. , It was observed that the increasing amount of the APG (or ADSAM or ATSAM) addition had almost no effect on the relative viscosity of dsDNA.…”

Section: Results and Discussionmentioning

confidence: 88%

“…They recorded a decrease in the guanine signal with the addition of the drug. Our another published work has been dedicated to deciphering the experimental and theoretical investigation of anticancer drug fludarabine-binding mechanism via multispectroscopic techniques, including UV absorption spectroscopy and thermal denaturation, fluorescence, and Fourier transform infrared (FTIR) spectroscopy, and electrochemical and viscosity measurement methods as well as molecular docking studies under physiological conditions . Our studies and literature search have shown that the binding mode between three compounds (APG, ADSAM, and ATSAM) and dsDNA is groove-binding as the dAdo peak current significantly decreases regularly with increasing compound (APG, ADSAM, or ATSAM) concentration and the anodic peak potential shifts to a more negative region.…”

Section: Results and Discussionmentioning

confidence: 99%

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Mechanism of Interactions of dsDNA Binding with Apigenin and Its Sulfamate Derivatives Using Multispectroscopic, Voltammetric, and Molecular Docking Studies

et al. 2021

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DNA binding investigations are critical for designing better pharmaceutical compounds since the binding of a compound to dsDNA in the minor groove is critical in drug discovery. Although only one in vitro study on the DNA binding mode of apigenin (APG) has been conducted, there have been no electrochemical and theoretical studies reported. We hereby report the mechanism of binding interaction of APG and a new class of sulfonamide-modified flavonoids, apigenin disulfonamide (ADSAM) and apigenin trisulfonamide (ATSAM), with deoxyribonucleic acid (DNA). This study was conducted using multispectroscopic instrumentation techniques, which include UV–vis absorption, thermal denaturation, fluorescence, and Fourier transform infrared (FTIR) spectroscopy, and electrochemical and viscosity measurement methods. Also, molecular docking studies were conducted at room temperature under physiological conditions (pH 7.4). The molecular docking studies showed that, in all cases, the lowest energy docking poses bind to the minor groove of DNA and the apigenin–DNA complex was stabilized by several hydrogen bonds. Also, π–sulfur interactions played a role in the stabilization of the ADSAM–DNA and ATSAM–DNA complexes. The binding affinities of the lowest energy docking pose (schematic diagram of table of content (TOC)) of APG–DNA, ADSAM–DNA, and ATSAM–DNA complexes were found to be −8.2, −8.5, and −8.4 kcal mol–1, respectively. The electrochemical binding constants K b were determined to be (1.05 × 105) ± 0.04, (0.47 × 105) ± 0.02, and (8.13 × 105) ± 0.03 for APG, ADSAM, and ATSAM, respectively (all of the tests were run in triplicate and expressed as the mean and standard deviation (SD)). The K b constants calculated for APG, ADSAM, and ATSAM are in harmony for all techniques. As a result of the incorporation of dimethylsulfamate groups into the APG structure, in the ADSAM–dsDNA and ATSAM–dsDNA complexes, in addition to hydrogen bonds, π–sulfur interactions have also contributed to the stabilization of the ligand–DNA complexes. This work provides new insights that could lead to the development of prospective drugs and vaccines.

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Section: Results and Discussionmentioning

confidence: 86%

Section: Results and Discussionmentioning

confidence: 86%

Section: Results and Discussionmentioning

confidence: 88%

Section: Results and Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Mechanism of Interactions of dsDNA Binding with Apigenin and Its Sulfamate Derivatives Using Multispectroscopic, Voltammetric, and Molecular Docking Studies

et al. 2021

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“…Intercalative binding of a drug with DNA offers a reduction in absorption intensity whereas enhancement in the absorption intensity would appear when a ligand undergoes a non-covalent (electrostatic or groove binding) mode of binding with DNA. [45] To further confirm the exact quenching mechanism UV-Visible absorption technique was employed. The absorption spectra of DNA were collected in the spectral range of 200-450 nm and a characteristic intense absorption band was observed at 260 nm for pure DNA.…”

Section: Uv-visible Absorption Experimentsmentioning

confidence: 99%

Synthesis and In vitro‐In silico Evaluation of Thiazolo‐triazole Hybrids as Anticancer Candidates

et al. 2023

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To meet the growing need for stable and clinically effective chemotherapeutic agents, herein, we have synthesized a series of acyl‐functionalized thiazolo[3,2‐b]‐[1,2,4]triazole derivatives in highly efficient and regioselective manner. The structure of newly synthesized regioisomeric products was unambiguously characterized by multinuclear 2D‐NMR [(1H−13C) HMBC, (1H−13C) HMQC] spectroscopic data. To assess the anticancer and pharmacokinetic profile of the synthesized compounds, we performed in silico, and ex vivo binding studies of compounds with calf‐thymus deoxyribonucleic acid (ct‐DNA) and bovine serum albumin (BSA), respectively, and also tested their efficacy against five human cancer cell lines. viz., MCF‐7 (breast cancer), BT‐474 (breast cancer), A549 (lung cancer), MOLT4 (acute lymphoblastic leukemia), and BxPC3 (pancreatic cancer). Compounds (2‐(4‐chlorophenyl)‐6‐methylthiazolo[3,2‐b][1,2,4]triazol‐5‐yl)(4‐fluorophenyl)methanone 6 l, (4‐chlorophenyl)(2‐(4‐chlorophenyl)‐6‐methylthiazolo[3,2‐b][1,2,4]triazol‐5‐yl)methanone 6 m and (2‐(4‐chlorophenyl)‐6‐methylthiazolo[3,2‐b][1,2,4]triazol‐5‐yl)(4‐methoxyphenyl) methanone 6 q exhibited excellent anticancer potential among the screened derivatives. Furthermore, ex‐vivo mechanistic investigations showed the static mode of quenching and moderate bindings between the ligand and biomolecules; DNA (Kq=2.01‐2.24*1012 M−1 s−1) and BSA (Kq=2.25‐.2.72*1012 M−1 s−1). Moreover, fluorescence displacement assay demonstrated a groove binding mode of interaction with ct‐DNA, which was supported by UV‐Visible absorption spectrum, circular dichroism, and viscosity analysis.

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A Transdermal Drug Delivery System Based on Nucleic Acid Nanomaterials for Skin Photodamage Treatment

et al. 2023

Adv Funct Materials

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Skin photodamage, which is induced by ultraviolet (UV) radiation, is a prevalent cause of skin damage. In this study, a transdermal drug delivery system is developed for the topical treatment of skin photodamage, which is composed of tetrahedral framework nucleic acids (tFNAs) and lipoic acid (LA). The tFNAs‐LA (TLA) nanocomposite exhibits excellent biocompatibility, as well as antioxidant, anti‐apoptotic, and anti‐inflammatory capabilities. tFNA, as a carrier, facilitates TLA for cell entry and skin penetration, while the loaded LA enhances the antioxidant and anti‐inflammatory capabilities. In photodamaged human dermal fibroblast (HDF), TLA promotes proliferation and migration while inhibiting apoptosis activation and reactive oxygen species production. Moreover, TLA modulates apoptosis‐related proteins and NF‐κB signaling pathways, increasing cellular secretion while suppressing inflammatory responses in photodamaged HDF cells. In the in vivo experiment, topical application of TLA promotes tissue healing in photodamaged skin, and regulates the expression of inflammation and collagen‐related proteins. It is suggested that the transdermal ability of TLA enables non‐invasive therapy for skin photodamage, highlighting the potential of employing nucleic acid‐based transdermal drug delivery systems for skin disease.

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Elucidation of binding interactions and mechanism of Fludarabine with dsDNA via multispectroscopic and molecular docking studies

Cited by 18 publications

References 27 publications

Mechanism of Interactions of dsDNA Binding with Apigenin and Its Sulfamate Derivatives Using Multispectroscopic, Voltammetric, and Molecular Docking Studies

Mechanism of Interactions of dsDNA Binding with Apigenin and Its Sulfamate Derivatives Using Multispectroscopic, Voltammetric, and Molecular Docking Studies

Synthesis and In vitro‐In silico Evaluation of Thiazolo‐triazole Hybrids as Anticancer Candidates

A Transdermal Drug Delivery System Based on Nucleic Acid Nanomaterials for Skin Photodamage Treatment

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