title: Design, synthesis and cytotoxic activities of scopoletin-isoxazole and scopoletin-pyrazole hybrids.
abstract: 12 novel scopoletin-isoxazole and scopoletin-pyrazole hybrids were designed, synthesized and their chemical structures were confirmed by HR-MS, IR,1H NMR and13C 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 IC50values below 20μM. 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 IC50values ranging from 8.76μM to 9.83μM and weak cytotoxicity with IC50value of 90.9μM 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.
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jinglin
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Na
authors.initials: N
authors.lastname: Bao
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Dongang
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China. Electronic address: chenli627@cpu.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China. Electronic address: sjbcpu@gmail.com.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Sun
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007555:Isoxazoles / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D011720:Pyrazoles / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D011758:Pyrroles / Q000494:pharmacology; D012603:Scopoletin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D000077210:Sunitinib
chemical_list: C000622942:6-methoxy-2-oxo-2H-chromen-7-yl 3-methyl-5-(4-nitrophenyl)isoxazole-4-carboxylate; D000970:Antineoplastic Agents; D007211:Indoles; D007555:Isoxazoles; D011720:Pyrazoles; D011758:Pyrroles; D012603:Scopoletin; D000077210:Sunitinib
keywords: Cytotoxic activity; Isoxazole; Pyrazole; Scopoletin