Design, synthesis and cytotoxic activities of scopoletin-isoxazole and scopoletin-pyrazole hybrids

作者：Shi, Wei; Hu, Jinglin; Bao, Na; Li, Dongang; Chen, Li^*; Sun, Jianbo^*

来源：Bioorganic & Medicinal Chemistry Letters, 2017, 27(2): 147-151.

DOI：10.1016/j.bmcl.2016.11.089

• Scopoletin
• Pyrazole
• Isoxazole
• Cytotoxic activity

12 novel scopoletin-isoxazole and scopoletin-pyrazole hybrids were designed, synthesized and their chemical structures were confirmed by HR-MS, IR, H-1 NMR and C-13 NMR spectra. The anticancer activities of the newly synthesized compounds were evaluated in vitro against three human cancer cell lines including HCT-116, Hun7 and SW620 by MTT assay. The screening results showed that six compounds (9a, 9c, 9d, 12a, 18b and 18d) exhibited potent cytotoxic activities with IC50 values below 20 mu M. Besides, we have further evaluated the growth inhibitory activities of six compounds against the human normal tissue cell lines HFL-1. Especially, compound 9d displayed significant anti-proliferative activity with IC50 values ranging from 8.76 mu M to 9.83 mu M and weak cytotoxicity with IC50 value of 90.9 mu M on normal cells HFL-1, which suggested that isoxazole-based hybrids of scopoletin were an effective chemical modification to improve the anticancer activity of scopoletin.

• 出版日期2017-1-15
• 单位中国药科大学