5-Substituted 3, 3′, 4′, 7-tetramethoxyflavonoids – A novel class of potent DNA triplex specific binding ligands

Rangel, Vanessa M.; Gu, L.C.; Chen, Guanglin; Chen, Qiao‐Hong; Xue, Liang

doi:10.1016/j.bmcl.2022.128608

Cited by 3 publications

(1 citation statement)

References 39 publications

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“…ITC is another solution phase method that measures the thermodynamic and stoichiometric values of binding interactions by detecting the heat absorbed or released during the binding process. ITC has been used for the investigation of the thermodynamic properties of many different biological macromolecules, including interactions between higher order DNA structures, proteins and small molecules for drug screening. − …”

Section: Resultsmentioning

confidence: 99%

Native Mass Spectrometric Insights into the Formation and Stability of DNA Triplexes

Klose,

Begbie,

Toronjo-Urquiza

et al. 2024

J. Am. Soc. Mass Spectrom.

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Deoxyribonucleic acid is a genetic biomacromolecule that contains the inherited information required to build and maintain a living organism. While the canonical duplex DNA structure is rigorously characterized, the structure and function of higher order DNA structures such as DNA triplexes are comparatively poorly understood. Previous literature has shown that these triplexes can form under physiological conditions, and native mass spectrometry offers a useful platform to study their formation and stability. However, experimental conditions including buffer salt concentration, pH, and instrumentation parameters such as ion mode can confound analysis by impacting the amount of triplex observed by mass spectrometry. Using model 30mer Y-type triplex sequences, we demonstrate the influence a range of experimental variables have on the detection of DNA triplex structures, informing suitable conditions for the study. When carefully considered conditions are used, mass spectrometry offers a powerful complementary tool for the analysis of higher order DNA assemblies.

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Section: Resultsmentioning

confidence: 99%

Native Mass Spectrometric Insights into the Formation and Stability of DNA Triplexes

Klose,

Begbie,

Toronjo-Urquiza

et al. 2024

J. Am. Soc. Mass Spectrom.

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5-Substituted Flavones—Another Class of Potent Triplex DNA-Specific Ligands as Antigene Enhancers

Gu,

Tran,

Rangel

et al. 2024

Molecules

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In the field of drug development, the quest for novel compounds that bind to DNA with high affinity and specificity never ends. In the present work, we report the newest development in this field, namely, triplex DNA-specific binding ligands based on the 5-substituted flavone scaffold in our lab. Biophysical studies showed that the newly synthesized flavone derivatives (depending on the side chains) bind to triplex DNA with binding affinities better than or similar to 5-substituted 3,3′,4′,7-tetramethoxyflavonoids. These compounds selectively stabilize triplex DNA while having little effect on duplex DNA, as verified by various biophysical methods. A detailed structural analysis suggested that the binding of these compounds to triplex DNA depends on the type of amino groups in the side chains and the length of the side chains. Viscosity studies suggested that these ligands bind to triplex DNA via intercalation. A representative ligand, compound 4b, showed a positive inhibitory effect on the activity of a restriction endonuclease (DraI) via ligand-mediated triplex formation. Several of these compounds exhibited excellent cytotoxicity toward various cancer cell lines (HT-29, HCT116, and HL-60), as indicated by the MTT assay. The work presented here is part of a continued effort from our laboratory to explore the novel structural motifs of natural product flavonoids for the development of triplex-specific ligands as antigene enhancers.

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Synthesis and biological properties of small molecules — ligands of non-canonical DNA and RNA structures

Abramovich,

Zaikina,

Barskaya

et al. 2024

RUSS CHEM REV

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Nucleic acids are important targets for many anticancer drugs. Apart from the canonical B-DNA double helix, DNA forms a number of non-canonical structures (G-quadruplexes, i-motifs, hairpins, triplexes, etc.), which play an important role in the regulation of biological processes. Binding to non-canonical DNA structures occurs mainly by π–π-stacking. Therefore, aromatic and heteroaromatic compounds, in particular fused poly-aromatic compounds (acridines, anthraquinones, carbazoles), porphyrins, benzothiazoles, benzimidazoles, pyridines, and quinolines, as well as their complexes are used as ligands for secondary structures. These ligands should possess not only high selectivity to non-canonical structures compared to double-stranded DNA, but also relatively high solubility and penetration through cell membranes. This review summarizes the achievements of 2020–2024 in the synthesis and biological studies of (hetero)arenes (acridines, anthraquinones, benzazoles, xanthones, porphyrins) and coordination compounds that have exhibited anticancer activity as a result of binding to non-canonical DNA or RNA structures. Ligands of various types of non-canonical nucleic acid structures (G-quadruplexes, i-motifs, triplexes, hairpins) are considered and their cytotoxic activity and structure–property relationships are compared. <br> The bibliography includes 166 references.

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5-Substituted 3, 3′, 4′, 7-tetramethoxyflavonoids – A novel class of potent DNA triplex specific binding ligands

Cited by 3 publications

References 39 publications

Native Mass Spectrometric Insights into the Formation and Stability of DNA Triplexes

Native Mass Spectrometric Insights into the Formation and Stability of DNA Triplexes

5-Substituted Flavones—Another Class of Potent Triplex DNA-Specific Ligands as Antigene Enhancers

Synthesis and biological properties of small molecules — ligands of non-canonical DNA and RNA structures

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