Biliavska Liubov, Pankivska Yuliia, Povnitsa Olga, Zagorodnya Svitlana, Gudz Ganna, Shermolovich Yuriy
Zabolotny Institute of Microbiology and Virology, National Academy of Sciences of Ukraine, 154, Zabolotnogo str., 03143 Kyiv, Ukraine.
Institute of Organic Chemistry, National Academy of Sciences of Ukraine, 5, Murmanska str., 02660 Kyiv, Ukraine.
Medicina (Kaunas). 2018 Nov 5;54(5):81. doi: 10.3390/medicina54050081.
A considerable increase in the levels of adenoviral diseases among both adults and children necessitate the development of effective methods for its prevention and treatment. The synthesis of the new fluorinated 1,2,3-triazoles, and the study of the mechanisms of their action, are promising for the development of efficient antiviral drugs of our time. Antiviral activity and cell cytotoxic effect of 2-(3-chlorotetrahydrofuran-2-yl)-4-tosyl-5-(perfluoropropyl)-1,2,3-triazole (G29) were determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. The influence of the compound on the infectivity of human adenovirus type 5 (HAdV-5) was carried out via the cytomorphology method. The influence of the compound on the cell cycle under a condition of adenovirus infection was studied using flow cytometric analysis of propidium iodide-stained cells. It was found that G29 suppressed HAdV-5 reproduction by 50% in concentrations of 37 μg/mL. Furthermore, the compound reduced the titer of virus obtained de novo, and inhibited HAdV-5 inclusion bodies formation by 84⁻90%. The use of fluorinated compounds under the conditions of adenovirus infection decreased the number of apoptotic cells by 11% and the number of cells in S phase by 21⁻42% compared to the profile of infected cells. The fluorinated compound G29 showed moderate activity against HAdV-5 based on several mechanisms. It led to the normalization of the life cycle of cells infected with adenovirus to the level of non-infected cells and caused the obstruction of HAdV-5 reproduction, inducing the formation of non-infectious virus progeny.
成人和儿童腺病毒疾病水平显著上升,因此有必要开发有效的预防和治疗方法。新型氟化1,2,3 - 三唑的合成及其作用机制研究,有望开发出当代高效的抗病毒药物。通过MTT(3-(4,5 - 二甲基噻唑 - 2 - 基)-2,5 - 二苯基四氮唑溴盐)法测定了2-(3 - 氯四氢呋喃 - 2 - 基)-4 - 甲苯磺酰基 - 5-(全氟丙基)-1,2,3 - 三唑(G29)的抗病毒活性和细胞细胞毒性作用。通过细胞形态学方法研究了该化合物对人5型腺病毒(HAdV - 5)感染性的影响。利用碘化丙啶染色细胞的流式细胞术分析,研究了该化合物在腺病毒感染条件下对细胞周期的影响。结果发现,G29在浓度为37μg/mL时可抑制HAdV - 5繁殖50%。此外,该化合物降低了新产生病毒的滴度,并抑制HAdV - 5包涵体形成达84⁻90%。与感染细胞的情况相比,在腺病毒感染条件下使用氟化化合物可使凋亡细胞数量减少11%,S期细胞数量减少21⁻42%。基于多种机制,氟化化合物G29对HAdV - 5表现出中等活性。它使感染腺病毒的细胞生命周期恢复到未感染细胞的水平,并导致HAdV - 5繁殖受阻,诱导形成无感染性的病毒后代。