Synthesis and antioxidant evaluation of desmethylxanthohumol analogs and their dimers.
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 using1H NMR,13C NMR and HRMS. The antioxidant activity of the new chalcone derivatives were evaluated in a PC12 cell model of H2O2-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 H2O2-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 EC50than that of gallic acid.
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.
Yuou
Y
Teng
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.
Xuzhe
X
Li
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.
Ke
K
Yang
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.
Xuehui
X
Li
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.
Zijun
Z
Zhang
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.
Luyao
L
Wang
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.
Zhijie
Z
Deng
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.
Binbin
B
Song
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.
Zhihong
Z
Yan
Université Pierre et Marie Curie-Paris 6, Institut Parisien de Chimie Moléculaire UMR CNRS 8232, 4 place Jussieu, 75005, Paris, France.
Yongmin
Y
Zhang
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. Electronic address: lukui@tust.edu.cn.
Kui
K
Lu
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. Electronic address: yupeng@tust.edu.cn.
Peng
P
Yu
D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D019281:Dimerization; D005419:Flavonoids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D008745:Methylation; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D011427:Propiophenones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats
D000975:Antioxidants; D005419:Flavonoids; D011427:Propiophenones; D006861:Hydrogen Peroxide; C104536:xanthohumol
Antioxidant; Chalcone; Desmethylxanthohumol; Dimer; Synthesis