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

Abstract

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 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 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 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.

• Authors: Hikaru Fukuda, Shinobu Sato, Tingting Zou, Sen Higashi, Osamu Takahashi, Manabu Habu, Masaaki Sasaguri, Kazuhiro Tominaga, Shigeori Takenaka, Hiroshi Takeuchi
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 50 Pg. 128323 (10 15 2021) ISSN: 1464-3405 [Electronic] England
• PMID: 34400300 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Imides
• Naphthalenes
• naphthalenediimide
• Cisplatin

Topics

• Antineoplastic Agents (chemistry, pharmacology)
• Bone Marrow Cells (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Circular Dichroism
• Cisplatin (pharmacology)
• G-Quadruplexes
• Humans
• Imides (chemistry, pharmacology)
• Keratinocytes (drug effects)
• Molecular Structure
• Naphthalenes (chemistry, pharmacology)
• Structure-Activity Relationship