Synthesis, anticancer activity and DNA-binding properties of novel 4-pyrazolyl-1,8-naphthalimide derivatives
- Bioorg Med Chem Lett. 2014 Jan 15;24(2):586-90. doi: 10.1016/j.bmcl.2013.12.014.
- 1. 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. Electronic address: [email protected].
- 2. Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China.
- 3. 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. Electronic address: [email protected].
- 4. 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.
- 5. Key Laboratory of Medicinal Chemistry and Molecular Diagnosis, Ministry of Education, Hebei University, Baoding 071002, China.
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.