Khomenko Tatyana M, Zarubaev Vladimir V, Orshanskaya Iana R, Kadyrova Renata A, Sannikova Victoria A, Korchagina Dina V, Volcho Konstantin P, Salakhutdinov Nariman F
Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia; Novosibirsk State University, Pirogova 2, Novosibirsk 630090, Russia.
Department of Chemotherapy, Influenza Research Institute, 15/17 Prof. Popova St., 197376 St. Petersburg, Russia.
Bioorg Med Chem Lett. 2017 Jul 1;27(13):2920-2925. doi: 10.1016/j.bmcl.2017.04.091. Epub 2017 Apr 29.
Compounds simultaneously carrying the monoterpene and coumarin moieties have been tested for cytotoxicity and inhibition of activity against influenza virus A/California/07/09 (H1N1)pdm09. The structure of substituents in the coumarin framework, as well as the structure and the absolute configuration of the monoterpenoid moiety, are shown to significantly influence the anti-influenza activity and cytotoxicity of the compounds under study. The compounds with a bicyclic pinane framework exhibit the highest selectivity indices (the ratios between the cytotoxicity and the active dose). The derivative of (-)-myrtenol 15c, which is characterized by promising activity, low cytotoxicity, and synthetic accessibility, has the greatest potential among this group of compounds. It exhibited the highest activity when added to the infected cell culture at early stages of viral reproduction.
同时携带单萜和香豆素部分的化合物已针对细胞毒性和对甲型流感病毒A/加利福尼亚/07/09（H1N1）pdm09的活性抑制进行了测试。结果表明，香豆素骨架中取代基的结构以及单萜部分的结构和绝对构型对所研究化合物的抗流感活性和细胞毒性有显著影响。具有双环蒎烷骨架的化合物表现出最高的选择性指数（细胞毒性与活性剂量之比）。（-）-桃金娘烯醇15c的衍生物具有良好的活性、低细胞毒性和合成可及性，在这组化合物中具有最大的潜力。在病毒繁殖早期添加到受感染细胞培养物中时，它表现出最高的活性。
