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New Xanthone Derivatives as Potent G-Quadruplex Binders for Developing Anti-Cancer Therapeutics

Roy, S and Maiti, B and Banerjee, N and Kaulage, MH and Muniyappa, K and Chatterjee, S and Bhattacharya, S (2022) New Xanthone Derivatives as Potent G-Quadruplex Binders for Developing Anti-Cancer Therapeutics. In: ACS Pharmacology and Translational Science .

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Official URL: https://doi.org/10.1021/acsptsci.2c00205


Xanthone is an important scaffold for various medicinally relevant compounds. However, it has received scant attention in the design of agents that are cytotoxic to cancer cells via targeting the stabilization of G-quadruplex (G4) nucleic acids. Specific G4 DNA recognition against double-stranded (ds) DNA is receiving epoch-making interest for the development of G4-mediated anticancer agents. Toward this goal, we have synthesized xanthone-based derivatives with various functionalized side-arm substituents that exhibited significant selectivity for G4 DNA as compared to dsDNA. The specific interaction has been demonstrated by performing various biophysical experiments. Based on the computational study as well as the competitive ligand binding assay, it is inferred that the potent compounds exhibit an end-stacking mode of binding with G4 DNA. Additionally, compound-induced conformational changes in the flanking nucleotides form the binding pocket for effective interaction. Selective action of the compounds on cancer cells suggests their effectiveness as potent anti-cancer agents. This study promotes the importance of structure-based screening approaches to get molecular insights for new scaffolds toward desired specific recognition of non-canonical G4 DNA structures. © 2023 American Chemical Society.

Item Type: Journal Article
Publication: ACS Pharmacology and Translational Science
Publisher: American Chemical Society
Additional Information: The copyright for this article belongs to American Chemical Society.
Keywords: cancer cells; G-quadruplex; genomic DNA; xanthone derivatives
Department/Centre: Division of Biological Sciences > Biochemistry
Division of Chemical Sciences > Organic Chemistry
Date Deposited: 25 Apr 2023 08:42
Last Modified: 25 Apr 2023 08:42
URI: https://eprints.iisc.ac.in/id/eprint/81396

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