设计并合成了具有双重功能的 NBD-荧光团的萘二酰亚胺衍生物，作为 G-四链体配体。
Design and synthesis of dual functional NBD-fluorophore-incorporated naphthalene diimide derivatives as G-quadruplex ligands.
机构信息
Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China; Department of Organic Chemistry, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China.
Key Laboratory of Structure-Based Drug Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China; Department of Organic Chemistry, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China.
出版信息
Bioorg Med Chem Lett. 2024 Oct 1;111:129903. doi: 10.1016/j.bmcl.2024.129903. Epub 2024 Jul 23.
Nitrobenzoxadiazole (NBD)-incorporated naphthalene diimide derivatives were designed and synthesized as candidates of antitumor agents with cytotoxicity against human pancreatic cancer cell MIA PaCa-2. Among these, compounds 1NND and 3NND exhibited fluorescent "turn-off" property toward human telomeric G-quadruplex (G4), which allows the direct measurement of dissociation constant (K) of ligands against G4 by fluorescence titration method. Notably, the compound 1NND not only exhibited great cytotoxic activity against MIA PaCa-2 with a half maximal inhibitory concentration (IC) of 77.9 nM, but also exhibited high affinity against G4 with K of 1.72 μM. Furthermore, the target binding properties were investigated by circular dichroism (CD) spectra and further studied by molecular docking methods.
硝基苯并二氮杂（NBD）结合的萘二酰亚胺衍生物被设计并合成，作为具有细胞毒性的抗肿瘤药物候选物，对人胰腺癌细胞 MIA PaCa-2 具有细胞毒性。在这些化合物中，化合物 1NND 和 3NND 对人类端粒 G-四链体（G4）表现出荧光“关闭”特性，这使得通过荧光滴定法直接测量配体与 G4 的解离常数（K）。值得注意的是，化合物 1NND 不仅对 MIA PaCa-2 表现出很强的细胞毒性，其半数最大抑制浓度（IC）为 77.9 nM，而且对 G4 也具有很高的亲和力，K 值为 1.72 μM。此外，通过圆二色性（CD）光谱研究了靶标结合特性，并通过分子对接方法进一步研究了其结合特性。
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