Capecitabine as a minor groove binder of DNA: molecular docking, molecular dynamics, and multi-spectroscopic studies

Zhang, Shuangshuang; Yang, Hongqin; Zhao, Ludan; Gan, Ruixue; Tang, Peixiao; Sun, Qiaomei; Xiong, Xiaopeng; Li, Hui

doi:10.1080/07391102.2018.1461137

Cited by 22 publications

(9 citation statements)

References 53 publications

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“…It has been demonstrated that the structure of the compounds is one of the most important factors that contribute to the DNA binding affinity. However, some factors of the ligands, including size, geometry, hydrophobicity, and hydrogen-bonding ability, can also influence the overall affinity [57].…”

Section: Uv-vis Absorption Spectroscopymentioning

confidence: 99%

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Zinc(II) Terpyridine Complexes: Substituent Effect on Photoluminescence, Antiproliferative Activity, and DNA Interaction

Liu

Jiang

et al. 2019

Molecules

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A series of ZnCl2 complexes (compounds 1–10) with 4′-(substituted-phenyl)-2,2′:6′,2′′-terpyridine that bears hydrogen (L1), p-methyl (L2), p-methoxy (L3), p-phenyl (L4), p-tolyl (L5), p-hydroxyl (L6), m-hydroxyl (L7), o-hydroxyl (L8), p-carboxyl (L9), or p-methylsulfonyl (L10) were prepared and then characterized by 1H NMR, electrospray mass-spectra (ESI-MS), IR, elemental analysis, and single crystal X-ray diffraction. In vitro cytotoxicity assay was used to monitor the antiproliferative activities against tumor cells. Absorption spectroscopy, fluorescence titration, circular dichroism spectroscopy, and molecular modeling studied the DNA interactions. All of the compounds display interesting photoluminescent properties and different maximal emission peaks due to the difference of the substituent groups. The cell viability studies indicate that the compounds have excellent antiproliferative activity against four human carcinoma cell lines, A549, Bel-7402, MCF-7, and Eca-109, with the lowest IC50 values of 0.33 (10), 0.66 (6), 0.37 (7), and 1.05 (7) μM, respectively. The spectrophotometric results reveal that the compounds have strong affinity binding with DNA as intercalator and induce DNA conformational transition. Molecular docking studies indicate that the binding is contributed by the π…π stacking and hydrogen bonds, providing an order of nucleotide sequence binding selectivity as ATGC > ATAT > GCGC. These compounds intercalate into the base pairs of the DNA of the tumor cells to affect their replication and transcription, and the process is supposed to play an important role in the anticancer mechanism.

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Section: Uv-vis Absorption Spectroscopymentioning

confidence: 99%

“…Fluorescent technique is widely used to obtain significant information regarding the interaction between a compound and a biomacromolecule, such as quenching constant, binding constant, and sites [57,64]. Accordingly, the technique was used to study the interaction between the compounds and DNA.…”

Section: Fluorescence Titrationmentioning

confidence: 99%

Zinc(II) Terpyridine Complexes: Substituent Effect on Photoluminescence, Antiproliferative Activity, and DNA Interaction

Liu

Jiang

et al. 2019

Molecules

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“… 44 On the other hand, in the case of groove or other nonclassical modes of binding, the twisting or bending of the double helix leads to a slight reduction of the length of the DNA, as a result of which a slight decrease in the viscosity is observed. 45 Figure S7 clearly displays the relative enhancement of viscosity of the DNA upon incubation with complex 1 . Another notable fact is that after the incremental addition of the complex to DNA, the viscosities of the ctDNA–complex 1 adducts increase following a linear pathway, and the pattern of growth follows that observed during DNA–EtBr conjugation.…”

Section: Results and Discussionmentioning

confidence: 99%

“…Generally, for intercalation binding, the insertion of the compound between the base pair increases the length of DNA, which leads to an enhancement of the viscosity of the bare macromolecule . On the other hand, in the case of groove or other nonclassical modes of binding, the twisting or bending of the double helix leads to a slight reduction of the length of the DNA, as a result of which a slight decrease in the viscosity is observed Figure S7 clearly displays the relative enhancement of viscosity of the DNA upon incubation with complex 1 .…”

Section: Results and Discussionmentioning

confidence: 99%

Response of Ancillary Azide Ligand in Designing a 1D Copper(II) Polymeric Complex along with the Introduction of High DNA- and HAS-Binding Efficacy, Leading to Impressive Anticancer Activity: A Compact Experimental and Theoretical Approach

Das¹,

Mukherjee

Islam

et al. 2022

ACS Omega

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A new versatile azide-bridged polymeric Cu(II) complex, namely, [Cu(L)(μ 1,3 -N 3 )] ∞ ( 1 ), was synthesized utilizing an N,N,O-donor piperidine-based Schiff base ligand ( E )-4-bromo-2-((2-(-1-yl)imino)methyl)phenol ( HL ), obtained via the condensation reaction of 1-(2-aminoethyl) piperidine and 5-bromo salicylaldehyde. The single-crystal X-ray diffraction analysis reveals that complex 1 consists of an end-to-end azido-bridged polymeric network, which is further rationalized with the help of a density functional theory (DFT) study. After routine characterization with a range of physicochemical studies, complex 1 is exploited to evaluate its biomedical potential. Initially, theoretical inspection with the help of a molecular docking study indicated the ability of complex 1 to effectively bind with macromolecules such as DNA and the human serum albumin (HSA) protein. The theoretical aspect was further verified by adopting several spectroscopic techniques. The electronic absorption spectroscopic analysis indicates a remarkable binding efficiency of Complex 1 with both DNA and HSA. The notable fluorescence intensity reduction of the ethidium bromide (EtBr)–DNA adduct, 4′,6-diamidino-2-phenylindole (DAPI)–DNA adduct, and HSA after the gradual addition of complex 1 authenticates its promising binding potential with the macromolecules. The retention of the canonical B form of DNA and α form of HSA during the association of complex 1 was confirmed by implementing a circular dichroism spectral study. The association ability of complex 1 with macromolecules further inspired us to inspect its impact on different cell lines such as HeLa (cervical cancer cell), PA1 (ovarian cancer cell), and HEK (normal cell). The dose-dependent and time-dependent in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay suggests an effective antiproliferative property of complex 1 with low toxicity toward the normal cell line. Finally, the anticancer activity of complex 1 toward carcinoma cell lines was analyzed by nuclear and cellular staining techniques, unveiling the cell death mechanism.

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“…A decreased binding constants at high temperatures suggested ABR's dissociation from ABR-ctDNA complex. In general terms a binding constant values in the range 10 6 to 10 8 M −1 suggested a strong binding affinity [29,30]. The binding constant values between ABR and ctDNA(Table 2) indicate a relatively strong binding interaction.…”

Section: Binding Constant and Binding Sitesmentioning

confidence: 89%

Interaction of an abiraterone with calf thymus DNA: Investigation with spectroscopic technique and modelling studies

Wani

Alsaif

Bakheit

et al. 2020

Bioorganic Chemistry

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Binding of toxic ligands to DNA could result in undesirable biological processes, such as carcinogenesis or mutagenesis. Binding mode of Abiraterone (ABR), a steroid drug and ctDNA(calf thymus DNA was investigated in this study using fluorescence and ultraviolet-visible spectroscopy. The probable prediction of binding and the type of interaction forces involved in the arrangement between ABR and ctDNA were explored through spectroscopic and molecular docking studies. The results indicated the binding of ABR to ctDNA in the minor groove. The binding constants were in the range of 1.35 × 10 6 -0.36× 10 6 L mol -1 at the studied temperatures.Fluorescence and spectrophotometric data suggested static quenching between ctDNA and ABR The endothermic values of thermodynamic parameters ΔH = -82.8 kJ mol −1 ; ΔS = -161 J mol −1 K −1 suggested that hydrogen bonding is the main force involved in binding ctDNA and ABR. In experimental studies the free binding energy at 298K was −34.9 kJ mol −1 with the relative binding energy ≈ −29.65 kJ mol −1 of docked structure. The Ksv obtained for ABR-KI was similar to that for ABR-ctDNA -KI demonstrating no protection by ctDNA against quenching effect of KI. Thus, suggesting involvement of groove binding between ABR and ctDNA. No change in the fluorescence intensity of ABR-ctDNA was observed in presence of NaCl. Thus, ruling out the involvement of electrostatic interaction. These studies could serve as new insights in understanding the mechanisms of toxicity, resistance and side effects of ABR.

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Capecitabine as a minor groove binder of DNA: molecular docking, molecular dynamics, and multi-spectroscopic studies

Cited by 22 publications

References 53 publications

Zinc(II) Terpyridine Complexes: Substituent Effect on Photoluminescence, Antiproliferative Activity, and DNA Interaction

Zinc(II) Terpyridine Complexes: Substituent Effect on Photoluminescence, Antiproliferative Activity, and DNA Interaction

Response of Ancillary Azide Ligand in Designing a 1D Copper(II) Polymeric Complex along with the Introduction of High DNA- and HAS-Binding Efficacy, Leading to Impressive Anticancer Activity: A Compact Experimental and Theoretical Approach

Interaction of an abiraterone with calf thymus DNA: Investigation with spectroscopic technique and modelling studies

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