title: Further discovery of caffeic acid derivatives as novel influenza neuraminidase inhibitors.
abstract: Eight series of compounds, each series containing two to five compounds were prepared by structural modifications of a lead, which was previously discovered as a mild influenza neuraminidase (NA) inhibitor. On the basis of the biological result, a detailed structure-activity relationship (SAR) was derived and discussed. Several caffeic acid derivatives that acted as non-competitive inhibitors were close or superior to the lead and also presented good antiviral activities in cells. Besides, it was interesting to find that modifications of the lead with different strategies could result in selective inhibition against N1 or N2. The preliminary docking analysis indicated that the 150-cavity of the enzymes played an important role in the selective inhibition.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, Jinan, Shandong 250012, PR China. Electronic address: yuanchaox623@aliyun.com.
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: Wenfang
authors.initials: W
authors.lastname: Xu
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002109:Caffeic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D053127:Influenza A Virus, H9N2 Subtype / Q000187:drug effects* / Q000201:enzymology*; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D002109:Caffeic Acids; D004791:Enzyme Inhibitors; D009439:Neuraminidase; C040048:caffeic acid
keywords: Caffeic acid; Influenza; Inhibitor; Neuraminidase