Substituent effects of cyclic naphthalene diimide on G-quadruplex binding and the inhibition of cancer cell growth

[摘要] Interaction of cyclic naphthalene diimide derivatives (cNDIs), 1-4, 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 1-4 has 10(6) M-1 order of binding affinity with the following order: 1 4 > 2 > 3 under both conditions. Meting temperature (T-m) 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 1-3 was correlated with their binding affinity under dilute condition. 3 showed specific growth inhibition of cancer cell line Ca9-22 at <0.03 mu M of IC50, with no inhibitory effect against normal bone marrow cells. 3, which has highest value of Delta H/Delta G, shows the highest inhibition ability for Ca9-22, carrying a highest expression level of telomerase mRNA.

[发布日期] 2021-10-15

[关键词] Cyclic naphthalene diimide;G-quadruplex binder;G-quartet DNA;Telomerase;Anti-cancer drug