title: Caffeic acid derivatives: a new type of influenza neuraminidase inhibitors.
abstract: Recently, many natural products, especially some plant-derived polyphenols have been found to exert antiviral effects against influenza virus and show inhibitory activities on neuraminidases (NAs). In our research, we took caffeic acid which contained two phenolic hydroxyl groups as the basic fragment to build a small compound library with various structures. The enzyme inhibition result indicated that some compounds exhibited moderate activities against NA and compound 15d was the best with IC50=7.2 μM and 8.5 μM against N2 and N1 NAs, respectively. The 3,4-dihydroxyphenyl group from caffeic acid was important for the activity according to the docking analysis. Besides, compound 15d was found to be a non-competitive inhibitor with Ki=11.5±0.25 μM by the kinetic study and also presented anti-influenza virus activity in chicken embryo fibroblast cells. It seemed promising to discover more potent NA inhibitors from caffeic acid derivatives to cope with influenza virus.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan, Shandong 250012, PR China. yuanchaox623@yahoo.cn
authors.forename: Yuanchao
authors.initials: Y
authors.lastname: Xie
authors.forename: Bing
authors.initials: B
authors.lastname: Huang
authors.forename: Kexiang
authors.initials: K
authors.lastname: Yu
authors.forename: Fangyuan
authors.initials: F
authors.lastname: Shi
authors.forename: Tianqi
authors.initials: T
authors.lastname: Liu
authors.forename: Wenfang
authors.initials: W
authors.lastname: Xu
mesh_terms: D000818:Animals; D002109:Caffeic Acids / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D002642:Chick Embryo; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000821:virology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000201:enzymology*; D053124:Influenza A Virus, H5N1 Subtype / Q000201:enzymology*; D007700:Kinetics; D008958:Models, Molecular; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D002109:Caffeic Acids; D004791:Enzyme Inhibitors; D009439:Neuraminidase; C040048:caffeic acid