2. Academic Validation
  3. Synthesis and antioxidant evaluation of desmethylxanthohumol analogs and their dimers

Synthesis and antioxidant evaluation of desmethylxanthohumol analogs and their dimers

  • Eur J Med Chem. 2017 Jan 5;125:335-345. doi: 10.1016/j.ejmech.2016.09.024.
Yuou Teng 1,  Xuzhe Li 1,  Ke Yang 1,  Xuehui Li 1,  Zijun Zhang 1,  Luyao Wang 1,  Zhijie Deng 1,  Binbin Song 1,  Zhihong Yan 1,  Yongmin Zhang 2,  Kui Lu 3,  Peng Yu 4
Affiliations

Affiliations

  • 1 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.
  • 2 Université Pierre et Marie Curie-Paris 6, Institut Parisien de Chimie Moléculaire UMR CNRS 8232, 4 place Jussieu, 75005, Paris, France.
  • 3 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: [email protected].
  • 4 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: [email protected].
PMID: 27688188 DOI: 10.1016/j.ejmech.2016.09.024
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 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 EC50 than that of gallic acid.

Keywords

Antioxidant; Chalcone; Desmethylxanthohumol; Dimer; Synthesis.

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