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Substituent effects of cyclic naphthalene diimide on G-quadruplex binding and the inhibition of cancer cell growth
Bioorganic & Medicinal Chemistry Letters ( IF 2.7 ) Pub Date : 2021-08-13 , DOI: 10.1016/j.bmcl.2021.128323
Hikaru Fukuda 1 , Shinobu Sato 2 , Tingting Zou 2 , Sen Higashi 3 , Osamu Takahashi 4 , Manabu Habu 4 , Masaaki Sasaguri 4 , Kazuhiro Tominaga 4 , Shigeori Takenaka 2 , Hiroshi Takeuchi 3
Affiliation  

Interaction of cyclic naphthalene diimide derivatives (cNDIs), 14, with TA-core and c-myc as G-quartet (G4) DNA was studied under dilute or molecular crowding condition. Binding study for TA-core based on an isothermal titration calorimetry showed that 14 has 106 M−1 order of binding affinity with the following order: 1 > 4 > 2 > 3 under both conditions. Meting temperature (Tm) of TA-core obtained from the temperature dependence of circular dichroism spectra shows that TA-core was most stabilized by 4, which is in agreement with the result of PCR stop assay and the stabilization effect for 13 was correlated with their binding affinity under dilute condition. 3 showed specific growth inhibition of cancer cell line Ca9-22 at <0.03 μM of IC50, with no inhibitory effect against normal bone marrow cells. 3, which has highest value of ΔH/ΔG, shows the highest inhibition ability for Ca9-22, carrying a highest expression level of telomerase mRNA.



中文翻译:

环萘二亚胺取代基对G-四链体结合及抑制癌细胞生长的影响

在稀释或分子拥挤条件下研究了环状萘二亚胺衍生物 (cNDI) 14与 TA-core 和 c - myc作为 G-四重 (G4) DNA 的相互作用。基于针对TA-芯结合研究的等温滴定量热法表明,1 - 4具有10 6 中号-1的以下顺序结合亲和力顺序:1  >  4  >  2  >  3两种条件下。从圆二色光谱的温度依赖性获得的TA-core的Meting温度(T m)表明TA-core最稳定4,这是在与PCR停止测定和用于稳定作用的结果是一致的1 - 3用稀的条件下的结合亲和力相关。图3显示在<0.03 μM的IC 50 下对癌细胞系Ca9-22的特异性生长抑制,对正常骨髓细胞没有抑制作用。图3中,ΔH/ΔG值最高,对Ca9-22的抑制能力最高,端粒酶mRNA表达量最高。

更新日期:2021-08-27
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