Design, synthesis and cytotoxic activities of scopoletin-isoxazole and scopoletin-pyrazole hybrids. Issue 2 (15th January 2017) - Shi, Wei
Graphical abstract: 12 novel scopoletin-pyrazole and scopoletin-isoxazole hybrids have been designed and synthesized. The in vitro anti-tumor activity screening results showed that the isoxazole-based hybrids of scopoletin are an effective chemical modification to improve the anticancer activity of scopoletin. Highlights: 12 novel scopoletin-isoxazole and scopoletin-pyrazole hybrids have been designed and synthesized. Their anti-tumor activities against HCT-116, Huh7 and SW 620 cells in vitro were evaluated. Compound9d displayed significant anti-proliferative activity on tumor cells and weak cytotoxicity on normal cells. Abstract: 12 novel scopoletin-isoxazole and scopoletin-pyrazole hybrids were designed, synthesized and their chemical structures were confirmed by HR-MS, IR, 1 H NMR and 13 C 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 and18d ) exhibited potent cytotoxic activities with IC50 values below 20 μM. Besides, we have further evaluated the growth inhibitory activities of six compounds against the human normal tissue cell lines HFL-1. Especially, compound9d displayed significant anti-proliferative activity with IC50 values ranging from 8.76 μM to 9.83 μM and weak cytotoxicity with IC50 value of 90.9 μM 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.