Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China; Key Laboratory of Medicinal Chemistry and Molecular Diagnosis, Ministry of Education, Hebei University, Baoding 071002, China.
Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China.
Bioorg Med Chem Lett. 2014 Jan 15;24(2):586-90. doi: 10.1016/j.bmcl.2013.12.014. Epub 2013 Dec 14.
A novel series of 4-pyrazolyl-1,8-naphthalimide derivatives have been designed and facilely synthesized. For anticancer activity in vitro, most of the compounds were found to be more toxic against human mammary cancer cells (MCF-7) than human cervical carcinoma cells (Hela) and human lung cancer cells (A549). Compounds 4i, 4h, 4b and 4a showed improved cytotoxic activity against MCF-7 cells over amonafide, in particular compounds 4i and 4h, the IC50 values of which against cell lines of MCF-7 were 0.51 μM and 0.79 μM, respectively. The DNA-binding properties of 4i were investigated by UV-vis, fluorescence, and Circular Dichroism (CD) spectroscopies and thermal denaturation. The results indicated that compound 4i as the DNA-intercalating agent exhibited middle binding affinity with CT-DNA.
我们设计并简便地合成了一系列新型的 4-吡唑基-1,8-萘酰亚胺衍生物。在体外抗癌活性方面，大多数化合物对人乳腺癌细胞（MCF-7）的毒性大于人宫颈癌细胞（Hela）和人肺癌细胞（A549）。化合物 4i、4h、4b 和 4a 对 MCF-7 细胞的细胞毒性活性均优于氨甲喋呤，特别是化合物 4i 和 4h，其对 MCF-7 细胞系的 IC50 值分别为 0.51 μM 和 0.79 μM。通过紫外可见光谱、荧光光谱和圆二色性（CD）光谱及热变性研究了 4i 的 DNA 结合性质。结果表明，化合物 4i 作为 DNA 嵌入剂，与 CT-DNA 具有中等的结合亲和力。
