（±）- 阿诺他汀A、B及其类似物的合成与抗氧化活性评价
Synthesis and anti-oxidant activity evaluation of (±)-Anastatins A, B and their analogs.
作者信息
Pan Guojun, Li Xuehui, Zhao Long, Wu Meng, Su Chao, Li Xuzhe, Zhang Yongmin, Yu Peng, Teng Yuou, Lu Kui
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.
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; Universite Pierre et Marie Curie-Paris 6, Institut Parisien de Chimie Moleculaire UMR CNRS 8232, 4 Place Jussieu, 75005, Paris, France.
出版信息
Eur J Med Chem. 2017 Sep 29;138:577-589. doi: 10.1016/j.ejmech.2017.06.054. Epub 2017 Jun 27.
Two novel flavonoids (±)-Anastatins A and B as well as 14 analogs, which containing a benzofuran moiety, were synthesized by using halogenation, Suzuki coupling reaction and an oxidation/Oxa-Michael reaction cascade as the key steps. The structures of the new flavonoids were confirmed by H NMR, C NMR and HRMS. The antioxidant activities of them as well as the key intermediates were evaluated by ferric reducing antioxidant power (FRAP) assay and the active compounds were evaluated in the PC12 cell model of hydrogen peroxide (HO)-induced oxidative damage. SAR studies suggested that, for in vitro antioxidant activity, aurone derivatives showed better bioactivity than flavone counterparts. However, cyclization to benzofuran and connecting the two conjugated parts as a whole conjugated system by a double bond diminished the in vitro antioxidant activity. Among them, the most potent compound 24c was significantly decreased HO-caused cell injury. The apoptotic rate (Annexin V) of HO-damaged PC12 cells was 60.7% while that of the compound 24c-treated cells decreased to 5.9% and 4.1% at 10 μM and 100 μM respectively.
以卤化、铃木耦合反应以及氧化/Oxa-迈克尔反应串联作为关键步骤，合成了两种新型黄酮类化合物（±）-Anastatins A和B以及14种含有苯并呋喃部分的类似物。通过氢核磁共振（H NMR）、碳核磁共振（C NMR）和高分辨质谱（HRMS）对新黄酮类化合物的结构进行了确认。采用铁还原抗氧化能力（FRAP）测定法评估了它们以及关键中间体的抗氧化活性，并在过氧化氢（HO）诱导的氧化损伤PC12细胞模型中对活性化合物进行了评估。构效关系研究表明，就体外抗氧化活性而言，噢哢衍生物显示出比黄酮类似物更好的生物活性。然而，环化形成苯并呋喃并通过双键将两个共轭部分连接成一个整体共轭体系会降低体外抗氧化活性。其中，最具活性的化合物24c显著降低了HO引起的细胞损伤。HO损伤的PC12细胞的凋亡率（膜联蛋白V）为60.7%，而化合物24c处理的细胞在10 μM和100 μM时凋亡率分别降至5.9%和4.1%。
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