新規環状ナフタレンジイミド誘導体の抗腫瘍活性の検討

• Published in: 日本薬理学会年会要旨集 p. 3-P-273
• Main Authors: 八井田, 昇, 冨永, 和宏, 福田, 晃, 竹中, 繁織, 佐藤, しのぶ, 笹栗, 正明, 東, 泉, 土生, 学, 竹内, 弘
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2022
• Subjects: cancer; chemotherapy
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.95.0_3-P-273

Telomerase is an enzyme that extends telomere sequences to the end of chromosome, and is well known to be overexpressed in more than 80% of cancer cells. Therefore, telomerase is expected as a target for developing novel anticancer drug. As the telomeric repeat sequences form characteristic G-quadruplex (G4) DNA structure, we have investigated the effects of novel compounds derived from G4-binding molecules on the tumor cells. In this study, we investigated the specificity of G4 DNA binding and the anticancer activity of cyclic naphthalene diimide derivatives (cNDIs).Binding of various cNDIs to G4 DNA was examined using isothermal titration calorimetry, circular dichroism spectrometry, and the PCR-stop assay. All the cNDIs showed G4 DNA binding with high specificity against duplex DNA. Then inhibitory activity of tumor cell growth was also examined using WST-8 assay. Among them, one cNDI with highest activity of tumor cell growth was also showed selective inhibition of tumor cells compared to cells from normal tissues. The compound induced cell apoptosis observed in the annexin V staining and caspase activation detected by Western blotting analysis. The results suggested that cNDIs are considered to be promising as new anticancer agents with improved cancer specificity.