Substituent effects of cyclic naphthalene diimide on G-quadruplex binding and the inhibition of cancer cell growth.
Substituent effects of cyclic naphthalene diimide on G-quadruplex binding and the inhibition of cancer cell growth.
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环萘二酰亚胺对 G-四链体结合和抑制癌细胞生长的取代作用。
DOI：
10.1016/j.bmcl.2021.128323
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
H.
中科院分区：
文献类型：
--
作者：
Fukuda;H.;Sato;S.;Zou;T.;Higashi;S.;Takahashi;O.;Habu;M.;Sasaguri;M.;Tominaga;K.;Takenaka;S.;Takeuchi;H.
研究了环状萘二酰亚胺衍生物（cNDIs）1 - 4与TA-核心和c-mycas G-四联体（G4）DNA在稀溶液或分子拥挤条件下的相互作用。基于等温滴定量热法的TA-核心结合研究表明，在两种条件下，1 - 4具有106 M − 1的结合亲和力，其顺序为：1> 4> 2> 3。圆二色光谱的温度依赖性分析表明，TA-核心的稳定性最好的是4，这与PCR终止实验的结果一致，并且1 - 3的稳定效果与它们在稀释条件下的结合亲和力有关。3对肿瘤细胞Ca9 - 22的生长抑制作用最强，IC50 <0. 03 μ M，对正常骨髓细胞无抑制作用; 3对肿瘤细胞Ca9 - 22的抑制作用最强，其Δ H/Δ G值最高，端粒酶mRNA表达水平最高。
Interaction of cyclic naphthalene diimide derivatives (cNDIs),1–4, with TA-core and c-mycas G-quartet (G4) DNA was studied under dilute or molecular crowding condition. Binding study for TA-core based on an isothermal titration calorimetry showed that1–4has 106M−1order of binding affinity with the following order:1>4>2>3under both conditions. Meting temperature (Tm) of TA-core obtained from the temperature dependence of circular dichroism spectra shows that TA-core was most stabilized by4, which is in agreement with the result of PCR stop assay and the stabilization effect for1–3was 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.