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• W3200712652 endingPage "116416" @default.
• W3200712652 startingPage "116416" @default.
• W3200712652 abstract "The development of ligands to stabilize G-quadruplexes (G4s) or induce G4s to transition from metastable topology to stable topology is a potential strategy for inhibiting cancer cell proliferation. In this study, a novel G-quadruplex (G4) ligand based on a naphthyridine scaffold with two indole pendants, L5-DA, is reported to convert hybrid to the parallel topology. Circular dichroism (CD) and fluorescence spectroscopies were used to investigate the interactions between L5-DA and G4s. The CD spectra revealed that the L5-DA induced the conformational conversion from hybrid topologies to parallel topologies with a melting temperature increase of more than 30 °C. According to Förster resonance energy transfer assays, the presence of excess duplex competitor had no effect on the ligand-induced stabilization of the hybrid topology, confirming the L5-DA's selectivity for G4s over ds26. With IC50 values of 4.3 μM, the ligand showed significant cytotoxicity against HeLa cells and effectively induced growth inhibition and apoptosis in HeLa cells. Immunofluorescence microscopy revealed an increase in BG4 foci in the presence of the L5-DA, confirming ligand-induced G4s stabilization in HeLa cells. According to these results, the combination of naphthyridine and indole scaffold was an effective design strategy for G4s stabilization and conformational conversion of metastable G4 topology for inhibiting cancer cell growth." @default.
• W3200712652 created "2021-09-27" @default.
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• W3200712652 date "2021-10-01" @default.
• W3200712652 modified "2023-09-26" @default.
• W3200712652 title "A naphthyridine-indole ligand for selective stabilization of G-quadruplexes and conformational conversion of hybrid topology" @default.
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• W3200712652 doi "https://doi.org/10.1016/j.bmc.2021.116416" @default.
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