title: 1,2,3-Triazole-containing derivatives of rupestonic acid: click-chemical synthesis and antiviral activities against influenza viruses.
abstract: Two series of rupestonic acid derivatives, (1-substituted-1H-1,2,3-triazol-4-yl)methyl 2-((5R,8S,8aS)-3,8-dimethyl-2-oxo-1,2,4,5,6,7,8,8a-octahydroazulen-5-yl)acrylate and N-(1-substituted-1H-1,2,3-triazol-4-yl)methyl 2-((5R,8S,8aS)-3,8-dimethyl-2-oxo-1,2,4,5,6,7,8,8a-octahydroazulen-5-yl)acrylamide were easily and efficiently synthesized via click chemistry. These compounds were tested for their in vitro activities against various strains of influenza A virus (H1N1, oseltamivir resistant H1N1, H3N2) and influenza B virus. The results showed that nine compounds were active against the H1N1 strain of influenza A virus and among them the best one 14a, was as active as the reference drugs, Oseltamivir and Ribavirin. Some of them were also active on the Oseltamivir resistant H1N1 strain. In regards to influenza B virus, twenty-one compounds over thirty were active and seven of them 7b, 8b, 9b, 10a, 11b, 12b, 13b showed better activity than Ribavirin. The structure-activity relationship of these compounds is discussed on the basis of each type of the viruses studied. Furthermore, four best representative compounds 7b, 10a, 12b and 14a were evaluated in a plaque assay experiment using MDCK cells and RBV as control compound and the results showed that 7b, 10a and 12b were better than RBV in inhibiting plaque formation, in good accordance with their anti-influenza B activities.
authors.affiliation: Key Laboratory of Plant Resources and Chemistry in Arid Regions, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing South Road 40-1, Urumqi, Xinjiang 830011, PR China; Université Paris Diderot, Sorbonne Paris Cité, ITODYS, UMR 7086 CNRS, 15 rue J-A de Baïf, 75205 Paris Cedex 13, France.
authors.forename: Yao-Wu
authors.initials: YW
authors.lastname: He
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, ITODYS, UMR 7086 CNRS, 15 rue J-A de Baïf, 75205 Paris Cedex 13, France; School of Light Industry and Chemical Engineering, Guangdong University of Technology, Guangzhou 510006, PR China. Electronic address: dong@univ-paris-diderot.fr.
authors.forename: Chang-Zhi
authors.initials: CZ
authors.lastname: Dong
authors.affiliation: Key Laboratory of Plant Resources and Chemistry in Arid Regions, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing South Road 40-1, Urumqi, Xinjiang 830011, PR China.
authors.forename: Jiang-Yu
authors.initials: JY
authors.lastname: Zhao
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, PR China.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Ma
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, PR China.
authors.forename: Yu-Huan
authors.initials: YH
authors.lastname: Li
authors.affiliation: Key Laboratory of Plant Resources and Chemistry in Arid Regions, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing South Road 40-1, Urumqi, Xinjiang 830011, PR China. Electronic address: haji@ms.xjb.ac.cn.
authors.forename: Haji Akber
authors.initials: HA
authors.lastname: Aisa
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D052176:Azulenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D057930:Click Chemistry; D009682:Magnetic Resonance Spectroscopy; D009975:Orthomyxoviridae / Q000145:classification / Q000187:drug effects*; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared; D014230:Triazoles / Q000737:chemistry*
chemical_list: D000998:Antiviral Agents; D052176:Azulenes; D012717:Sesquiterpenes; D014230:Triazoles; C057488:rupestonic acid
keywords: 1,2,3-Triazole; Click chemistry; Influenza virus; Rupestonic acid