去甲基黄腐酚类似物及其二聚体的合成与抗氧化性能评价

Synthesis and antioxidant evaluation of desmethylxanthohumol analogs and their dimers.

作者信息

Teng Yuou, Li Xuzhe, Yang Ke, Li Xuehui, Zhang Zijun, Wang Luyao, Deng Zhijie, Song Binbin, Yan Zhihong, Zhang Yongmin, Lu Kui, Yu Peng

机构信息

China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, Key Laboratory of Industrial Fermentation Microbiology of Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, Tianjin University of Science and Technology, Tianjin, 300457, China.

Université Pierre et Marie Curie-Paris 6, Institut Parisien de Chimie Moléculaire UMR CNRS 8232, 4 place Jussieu, 75005, Paris, France.

出版信息

Eur J Med Chem. 2017 Jan 5;125:335-345. doi: 10.1016/j.ejmech.2016.09.024. Epub 2016 Sep 13.

DOI:10.1016/j.ejmech.2016.09.024

PMID:27688188

Abstract

Four ring-closed analogs of natural prenylated chalcone desmethylxanthohumol (1) and their dimers were synthesized from the commercially available 1-(2,4,6-trihydroxyphenyl)ethan-1-one in five and six linear steps, respectively. The structures of the eight new derivatives were confirmed usingH NMR, C NMR and HRMS. The antioxidant activity of the new chalcone derivatives were evaluated in a PC12 cell model of HO-induced oxidative damage. The SAR studies suggested that the catechol motif was essential for the antioxidant activity. Moreover, the dimers showed better antioxidant activity than their corresponding monomers did. Among them, compound 14d was the most potent and increased PC12 cell viability from 25% to 85%. Flow cytometric analysis showed that compound 14d, the most potent compound, decreased the apoptotic PC12 cell percentage and significantly reduced the LDH release and 8-OHdG generation but increased the GSH levels in HO-treated PC12 cells. Furthermore, compound 14d had a higher FRAP value than that of gallic acid. It also reduced the stable ABTS free radical with a lower EC than that of gallic acid.

摘要

从市售的1-(2,4,6-三羟基苯基)乙-1-酮分别经五步和六步线性反应合成了天然异戊烯基查耳酮去甲基黄腐酚(1)的四种环化类似物及其二聚体。通过¹H NMR、¹³C NMR和HRMS对这八种新衍生物的结构进行了确证。在HO诱导的氧化损伤的PC12细胞模型中评估了新查耳酮衍生物的抗氧化活性。构效关系研究表明邻苯二酚基序对抗氧化活性至关重要。此外，二聚体的抗氧化活性优于其相应的单体。其中，化合物14d活性最强，可使PC12细胞活力从25%提高到85%。流式细胞术分析表明，活性最强的化合物14d降低了凋亡PC12细胞的百分比，显著降低了乳酸脱氢酶释放和8-羟基脱氧鸟苷生成，但提高了HO处理的PC12细胞中的谷胱甘肽水平。此外，化合物14d的铁离子还原抗氧化能力(FRAP)值高于没食子酸。它还以比没食子酸更低的半数有效浓度(EC)还原稳定的ABTS自由基。