Shi Wei, Hu Jinglin, Bao Na, Li Dongang, Chen Li, Sun Jianbo
Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
Bioorg Med Chem Lett. 2017 Jan 15;27(2):147-151. doi: 10.1016/j.bmcl.2016.11.089. Epub 2016 Dec 1.
12 novel scopoletin-isoxazole and scopoletin-pyrazole hybrids were designed, synthesized and their chemical structures were confirmed by HR-MS, IR, H NMR and 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 and 18d) exhibited potent cytotoxic activities with IC values 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 IC values ranging from 8.76μM to 9.83μM and weak cytotoxicity with IC value 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.
设计并合成了12种新型东莨菪亭-异恶唑和东莨菪亭-吡唑杂合物，其化学结构通过高分辨质谱（HR-MS）、红外光谱（IR）、氢核磁共振谱（H NMR）和碳核磁共振谱（C NMR）得以确认。采用MTT法在体外评估了新合成化合物对包括HCT-116、Hun7和SW620在内的三种人类癌细胞系的抗癌活性。筛选结果表明，六种化合物（9a、9c、9d、12a、18b和18d）表现出强效细胞毒性活性，IC值低于20μM。此外，我们进一步评估了六种化合物对人类正常组织细胞系HFL-1的生长抑制活性。特别是，化合物9d表现出显著的抗增殖活性，IC值在8.76μM至9.83μM之间，对正常细胞HFL-1的细胞毒性较弱，IC值为90.9μM，这表明基于异恶唑的东莨菪亭杂合物是提高东莨菪亭抗癌活性的有效化学修饰。
