Formation and stabilization of the telomeric antiparallel G-quadruplex and inhibition of telomerase by novel benzothioxanthene derivatives with anti-tumor activity

Scientific Reports
Wen ZhangYan Xu

Abstract

G-quadruplexes formed in telomeric DNA sequences at human chromosome ends can be a novel target for the development of therapeutics for the treatment of cancer patients. Herein, we examined the ability of six novel benzothioxanthene derivatives S1-S6 to induce the formation of and stabilize an antiparallel G-quadruplex by EMSA, UV-melting and CD techniques and the influence of S1-S6 on A549 and SGC7901 cells through real-time cell analysis, wound healing, trap assay methods. Results show that six compounds could differentially induce 26 nt G-rich oligonucleotides to form the G-quadruplex with high selectivity vs C-rich DNA, mutated DNA and double-stranded DNA, stabilize it with high affinity, promote apoptosis and inhibit mobility and telomerase activity of A549 cells and SGC7901 cells. Especially, S1, S3, S4 displayed stronger abilities, of which S3 was the most optimal with the maximum ΔTm value being up to 29.8 °C for G-quadruplex, the minimum IC50 value being 0.53 μM and the maximum cell inhibitory rate being up to 97.2%. This study suggests that this type of compounds that induce the formation of and stabilize the telomeric antiparallel G-quadruplex, and consequently inhibit telomerase activity, leading to cell apoptosis, ...Continue Reading

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Citations

Mar 13, 2018·Nucleosides, Nucleotides & Nucleic Acids·Jeremy E B McCallumBlake A Titterington
Feb 23, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Pallavi ChilkaBhaskar Datta
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Jun 28, 2019·Journal of the American Chemical Society·Cosimo DucaniAlessio Terenzi
Sep 3, 2021·Neuro-oncology·Elisa AquilantiMatthew Meyerson

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Datasets Mentioned

BETA
SGC7901

Methods Mentioned

BETA
electrophoretic
circular dichroism
nuclear
x-ray crystallography
X-ray
NMR
electrophoresis
column chromatography
PCR

Software Mentioned

RTCA

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