Design, synthesis and cytotoxic activities of scopoletin-isoxazole and scopoletin-pyrazole hybrids. Issue 2 (15th January 2017)

• Record Type: Journal Article
• Authors: Shi, Wei; Hu, Jinglin; Bao, Na; Li, Dongang; Chen, Li; Sun, Jianbo
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 2(2017)
• Page Start: 147
• Page End: 151
• Publication Date: 2017-01-15
• Subjects: Scopoletin -- Pyrazole -- Isoxazole -- Cytotoxic activity; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.11.089
• Languages: English
• ISSNs: 0960-894X

Abstract

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.