Carbazole ligands as c-myc G-quadruplex binders

Głuszyńska, Agata; Juskowiak, Bernard; Kuta-Siejkowska, Martyna; Hoffmann, Marcin; Haider, Shozeb

doi:10.1016/j.ijbiomac.2018.03.135

Cited by 33 publications

(30 citation statements)

References 114 publications

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“…The hydrophobic environment inside the G-quadruplex c-KIT 1 protects the ligand from quenching by polar water molecules and they recover their fluorescence [ 82 , 83 , 84 , 85 ]. In accordance with previous observations no plateau was observed for titration plots and the experiments were conducted until the changes in fluorescence spectra were insignificantly small [ 71 ]. Figure 4 A–C and Figure S2 (ESI) show the fluorescence spectra and binding plots for tested ligands 1 – 3 in the presence of various concentrations of GQ c-KIT 1.…”

Section: Resultssupporting

confidence: 87%

“…Recently, we have been interested in carbazole ligands interacting with G-quadruplexes formed by oligonucleotides with sequences corresponding to promoter regions of oncogenes [ 71 ]. The tested compounds 1 – 3 have carbazole skeletons containing a heterocyclic benzothiazolium moiety, a C=C double bond and additional substituents ( Figure 1 ).…”

Section: Resultsmentioning

confidence: 99%

“…The tested compounds 1 – 3 have carbazole skeletons containing a heterocyclic benzothiazolium moiety, a C=C double bond and additional substituents ( Figure 1 ). All these structural elements of the compounds may affect their potential biological properties and influence the stability of c-KIT 1 G-quadruplex [ 70 , 71 , 72 , 73 , 74 , 75 , 76 ].…”

Section: Resultsmentioning

confidence: 99%

“…We have been interested to check the effect of carbazole ligands on stabilization of promoter G-quadruplex DNAs c-MYC and c-KIT [ 71 ]. UV-Vis and fluorescence experiments were conducted to find spectral effects for the ligands 1 – 3 bound to GQs DNA and the binding constants of the ligands with c-MYC and c-KIT GQs.…”

Section: Resultsmentioning

confidence: 99%

“…Recently, we have reported carbazole derivatives that can specifically stabilize c-MYC G-quadruplex DNA having a parallel topology [ 71 ]. Herein, we describe UV-Vis, fluorescence and CD spectra and molecular modeling of three carbazole ligands complexed with c-KIT 1 G-quadruplex.…”

Section: Introductionmentioning

confidence: 99%

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Carbazole Derivatives’ Binding to c-KIT G-Quadruplex DNA

et al. 2018

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The binding affinities of three carbazole derivatives to the intramolecular G-quadruplex (GQ) DNA formed by the sequence 5′-AGGGAGGGCGCTGGGAGGAGGG-3′, derived from the c-KIT 1 oncogene region, were investigated. All carbazole cationic ligands that differed in the substituents on the nitrogen atom were able to stabilize G-quadruplex, as demonstrated using UV-Vis, fluorescence and CD spectroscopic techniques as well as molecular modeling. The spectrophotometric titration results showed spectral features characteristic of these ligands-bathochromic shifts and initial hypochromicity followed by hyperchromicity at higher GQ concentrations. All free carbazole ligands exhibited modest fluorescent properties, but after binding to the DNA the fluorescence intensity increased significantly. The binding affinities of carbazole ligands to the c-KIT 1 DNA were comparable showing values in the order of 105 M−1. Molecular modeling highlights the differences in interactions between each particular ligand and studied G-quadruplex, which potentially influenced binding strength. Obtained results relevant that all three investigated ligands have stabilization properties on studied G-quadruplex.

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Section: Resultssupporting

confidence: 87%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Carbazole Derivatives’ Binding to c-KIT G-Quadruplex DNA

et al. 2018

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DPA‐Substituted Carbazole Derivative as a Fluorescent Ligand for G4 DNA

Wang

Zhang

Luo

et al. 2022

Chemistry & Biodiversity

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Herein a conjugated dipicolylamine/carbazole (Car‐DPA) molecule was designed and synthesized to enhance the performance for the application as a G4 fluorescent ligand. This ligand has been found to display distinct and specific fluorescence enhancements in the presence of various G4 DNA structures, but limited with ssDNA or dsDNAs. The detail binding characteristics of the ligand with c‐MYC G4 DNA were investigated by fluorescence, UV/VIS absorption, CD spectroscopy, and molecular docking. The present study demonstrated that Car‐DPA bound to c‐MYC G4s with a two‐step complex formation, in which the binding mode appeared to be end‐stacking. Confocal fluorescence images indicated that ligand Car‐DPA could locate in nucleus, which is quite prominent from the cellular internalization studies.

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Insights from Binding on Quadruplex Selective Carbazole Ligands

Müller

Saha

Panda

et al. 2021

Chemistry A European J

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Polymorphic G-quadruplex (G4) secondary DNA structures have received increasing attention in medicinal chemistry owing to their key involvement in the regulation of the maintenance of genomic stability, telomere length homeostasis and transcription of important proto-oncogenes. Different classes of G4 ligands have been developed for the potential treatment of several human diseases. Among them, the carbazole scaffold with appropriate side chain appendages has attracted much interest for designing G4 ligands. Because of its large and rigid π-conjugation system and ease of functionalization at three different positions, a variety of carbazole derivatives have been synthesized from various natural or synthetic sources for potential applications in G4based therapeutics and biosensors. Herein, we provide an updated close-up of the literatures on carbazole-based G4 ligands with particular focus given on their detailed binding insights studied by NMR spectroscopy. The structure-activity relationships and the opportunities and challenges of their potential applications as biosensors and therapeutics are also discussed. This review will provide an overall picture of carbazole ligands with remarkable G4 topological preference, fluorescence properties and significant bioactivity; portraying carbazole as a very promising scaffold for assembling G4 ligands with a range of novel functional applications.

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Carbazole ligands as c-myc G-quadruplex binders

Cited by 33 publications

References 114 publications

Carbazole Derivatives’ Binding to c-KIT G-Quadruplex DNA

Carbazole Derivatives’ Binding to c-KIT G-Quadruplex DNA

DPA‐Substituted Carbazole Derivative as a Fluorescent Ligand for G4 DNA

Insights from Binding on Quadruplex Selective Carbazole Ligands

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