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接头结构中含有酰胺或/和1,2,3-三唑部分的新型尿苷糖缀合物的抗蜱传脑炎病毒活性

Anti-Tick-Borne Encephalitis Virus Activity of Novel Uridine Glycoconjugates Containing Amide or/and 1,2,3-Triazole Moiety in the Linker Structure.

作者信息

Brzuska Gabriela, Pastuch-Gawolek Gabriela, Krawczyk Monika, Szewczyk Boguslaw, Krol Ewelina

机构信息

Department of Recombinant Vaccines, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Abrahama 58, 80-307 Gdansk, Poland.

Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Faculty of Chemistry, Silesian University of Technology, Krzywoustego 4, 44-100 Gliwice, Poland.

出版信息

Pharmaceuticals (Basel). 2020 Dec 13;13(12):460. doi: 10.3390/ph13120460.

Abstract

Tick-borne encephalitis virus (TBEV) transmitted by ticks is a pathogen of great medical importance. As still no effective antiviral treatment is available, in the present study, a series of uridine glycoconjugates containing amide or/and 1,2,3-triazole moiety in the linker structure was synthesized and evaluated for the antiviral activity against two strains of TBEV: a highly virulent Hypr strain and less virulent Neudoerfl strain, using standardized previously in vitro assays. Our data have shown that four compounds from the series () possess strong activity against both TBEV strains. The half maximal inhibitory concentration (IC) values of compounds were between 15.1 and 3.7 μM depending on the virus strain, which along with low cytotoxicity resulted in high values of the selectivity index (SI). The obtained results suggest that these compounds may be promising candidates for further development of new therapies against flaviviruses.

摘要

蜱传脑炎病毒(TBEV)通过蜱传播,是一种具有重大医学意义的病原体。由于目前仍没有有效的抗病毒治疗方法,在本研究中,合成了一系列在连接结构中含有酰胺或/和1,2,3-三唑部分的尿苷糖缀合物,并使用先前标准化的体外试验评估了其对两种TBEV毒株的抗病毒活性:高毒力的Hypr毒株和低毒力的Neudoerfl毒株。我们的数据表明,该系列中的四种化合物对两种TBEV毒株均具有强大的活性。化合物的半数最大抑制浓度(IC)值在15.1至3.7μM之间,具体取决于病毒毒株,再加上低细胞毒性,导致选择性指数(SI)值较高。所得结果表明,这些化合物可能是进一步开发抗黄病毒新疗法的有前景的候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cdcf/7764612/05d1bd847a83/pharmaceuticals-13-00460-g001.jpg

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