简单的苝相关化合物作为抑制蜱传脑炎病毒繁殖的物质。

Simplistic perylene-related compounds as inhibitors of tick-borne encephalitis virus reproduction.

机构信息

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow 117997, Russia; Department of Chemistry, Lomonosov Moscow State University, Moscow 119991, Russia; Department of Biology and Biotechnology, National Research University Higher School of Economics, Moscow 117312, Russia.

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow 117997, Russia; FSBSI «Chumakov FSC R&D IBP RAS», Moscow 108819, Russia.

出版信息

Bioorg Med Chem Lett. 2020 May 15;30(10):127100. doi: 10.1016/j.bmcl.2020.127100. Epub 2020 Mar 9.

DOI:10.1016/j.bmcl.2020.127100

PMID:32199731

Abstract

Rigid amphipathic fusion inhibitors are potent broad-spectrum antivirals based on the perylene scaffold, usually decorated with a hydrophilic group linked via ethynyl or triazole. We have sequentially simplified these structures by removing sugar moiety, then converting uridine to aniline, then moving to perylenylthiophenecarboxylic acids and to perylenylcarboxylic acid. All these polyaromatic compounds, as well as antibiotic heliomycin, still showed pronounced activity against tick-borne encephalitis virus (TBEV) with limited toxicity in porcine embryo kidney (PEK) cell line. 5-(Perylen-3-yl)-2-thiophenecarboxylic acid (5a) showed the highest antiviral activity with 50% effective concentration of approx. 1.6 nM.

摘要

刚性两亲融合抑制剂是基于苝骨架的强效广谱抗病毒药物，通常通过乙炔基或三唑连接一个亲水基团进行修饰。我们已通过去除糖部分、将尿嘧啶转化为苯胺、然后转变为苝基噻吩羧酸和苝基羧酸的方式，逐步简化了这些结构。所有这些多环芳烃化合物以及抗生素 Helicomycin 仍然对蜱传脑炎病毒（TBEV）表现出明显的活性，同时在猪胚肾（PEK）细胞系中的毒性有限。5-（苝-3-基）-2-噻吩羧酸（5a）显示出最高的抗病毒活性，其 50%有效浓度约为 1.6 nM。