Zarubaev Vladimir V, Morkovnik Anatolii S, Divaeva Liudmila N, Karpinskaya Liubov' A, Borodkin Gennadii S
Influenza Research Institute, St. Petersburg, Russia.
Southern Federal University, Rostov-on-Don, Russia.
Bioorg Med Chem. 2016 Nov 15;24(22):5796-5803. doi: 10.1016/j.bmc.2016.09.036. Epub 2016 Sep 15.
A series of 1,3-disubstituted 2-iminobenzimidazolines as well as a number of their tautomeric analogs were synthesized. The synthesized compounds were tested for their cytotoxicity against MDCK cells and for inhibiting activity against influenza virus A/California/07/09 (H1N1)pdm09. Based on the results obtained, 50% cytotoxic concentration (CC), 50% inhibiting concentration (IC) and selectivity index (SI) were calculated for each compound. It was found that some of synthesized benzimidazole derivatives (7 of 22, 32%) possess strong virus-inhibiting activity against pandemic influenza virus (IC's in low micromolar range) with quite moderate cytotoxicity (CC in the range of thousands micromoles). Due to their high selectivity (highest SI's=50-83) these compounds are of significant interest for further in vivo experiments as well as for further structural optimization and drug development.
合成了一系列1,3 - 二取代的2 - 亚氨基苯并咪唑啉及其许多互变异构类似物。测试了合成化合物对MDCK细胞的细胞毒性以及对甲型流感病毒A/加利福尼亚/07/09（H1N1）pdm09的抑制活性。根据所得结果，计算了每种化合物的50％细胞毒性浓度（CC）、50％抑制浓度（IC）和选择性指数（SI）。发现一些合成的苯并咪唑衍生物（22种中的7种，32％）对大流行性流感病毒具有很强的病毒抑制活性（IC在低微摩尔范围内），且细胞毒性相当适中（CC在数千微摩尔范围内）。由于它们具有高选择性（最高SI = 50 - 83），这些化合物对于进一步的体内实验以及进一步的结构优化和药物开发具有重要意义。
