Synthesis, G-Quadruplex DNA binding and cytotoxic properties of naphthalimide substituted styryl dyes.,Bioorganic & Medicinal Chemistry

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Synthesis, G-Quadruplex DNA binding and cytotoxic properties of naphthalimide substituted styryl dyes.
Bioorganic & Medicinal Chemistry ( IF 3.3 ) Pub Date : 2020-01-18 , DOI: 10.1016/j.bmc.2020.115325
Ming-Qi Wang ₁ , Yi-Fan Liao ₁ , Shu-Hui Zhang ₁ , Quan-Qi Yu ₁ , Jin-Qiu Huang ₁

Affiliation

G-Quadruplex DNAs, formed by G-rich DNA sequences in human genes, are promising targets for design of cancer drugs. In this study, two naphthalimide substituted styryl dyes with different sizes of aromatic groups were synthesized. The spectral analysis showed that the dye X-2 with a large aromatic group formed aggregates in buffer solution displaying very weak fluorescence intensity, and disaggregated in the presence of G-Quadruplex DNAs with large intensity enhancements (up to ~1800 fold). Moreover, X-2 displayed good selectivity to G-Quadruplex DNAs. In contrast, dye X-3 with the smaller aromatic group had much lower fluorescence enhancements and poor selectivity to G-Quadruplex DNAs, suggesting that the suitably sized aromatic ring was essential for the interaction with G-Quadruplex. Further binding studies suggested that X-2 mainly bound on G-quartet surface through end-stacking mode. Cytotoxicity assay showed that both of the two dyes showed good anti-proliferative activities against the cancer cell lines and less cytotoxicity in non-malignant cell lines, which were better than a standard drug 5-fluorouracil. In addition, living cell imaging was also studied and demonstrated the potential applications of the new dye X-2 in bioassays and cell imaging.

中文翻译：

萘二甲酰亚胺取代的苯乙烯基染料的合成，G-四链体DNA结合和细胞毒性。

由人类基因中富含G的DNA序列形成的G-四链体DNA是设计癌症药物的有希望的目标。在这项研究中，合成了两种具有不同芳族基团大小的萘二甲酰亚胺取代的苯乙烯基染料。光谱分析表明，具有较大芳族基团的染料X-2在缓冲溶液中形成聚集体，显示非常弱的荧光强度，并在存在强度增强较大（高达1800倍）的G-Quadruplex DNA时分解。此外，X-2对G-四链体DNA具有良好的选择性。相反，具有较小芳族基团的染料X-3的荧光增强作用低得多，并且对G-Quadruplex DNA的选择性差，这表明适当大小的芳环对于与G-Quadruplex相互作用至关重要。进一步的结合研究表明，X-2主要通过末端堆积模式结合在G四重表面上。细胞毒性试验表明，两种染料均对癌细胞系表现出良好的抗增殖活性，在非恶性细胞系中的细胞毒性较小，优于标准药物5-氟尿嘧啶。此外，还研究了活细胞成像，并证明了新型染料X-2在生物测定和细胞成像中的潜在应用。

更新日期：2020-01-21

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