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.
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.
Eur J Med Chem. 2014 Apr 9;76:245-55. doi: 10.1016/j.ejmech.2014.02.029. Epub 2014 Feb 11.
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.
通过点击化学，我们很容易且高效地合成了两个鲁皮托尼酸衍生物系列：（1-取代-1H-1,2,3-三唑-4-基）甲基 2-（（5R,8S,8aS）-3,8-二甲基-2-氧代-1,2,4,5,6,7,8,8a-八氢薁-5-基）丙烯酸酯和 N-（1-取代-1H-1,2,3-三唑-4-基）甲基 2-（（5R,8S,8aS）-3,8-二甲基-2-氧代-1,2,4,5,6,7,8,8a-八氢薁-5-基）丙烯酰胺。这些化合物被测试了它们对各种流感 A 病毒（H1N1、奥司他韦耐药 H1N1、H3N2）和流感 B 病毒株的体外活性。结果表明，有 9 种化合物对 H1N1 流感 A 病毒株具有活性，其中最好的化合物 14a 与对照药物奥司他韦和利巴韦林活性相当。其中一些化合物对奥司他韦耐药 H1N1 株也具有活性。在流感 B 病毒方面，有超过 30 种的 21 种化合物具有活性，其中 7b、8b、9b、10a、11b、12b、13b 7 种化合物的活性优于利巴韦林。基于所研究的每种病毒的类型，讨论了这些化合物的构效关系。此外，还使用 MDCK 细胞和 RBV 作为对照化合物，在蚀斑试验中评估了四个最具代表性的化合物 7b、10a、12b 和 14a，结果表明，7b、10a 和 12b 在抑制蚀斑形成方面优于 RBV，这与它们的抗流感 B 活性一致。
