Ural Federal University Named After the First President of Russia B. N. Yeltsin, Department of Organic and Biomolecular Chemistry, 620002, 19 Mira St., Yekaterinburg, Russian Federation; Institute of Organic Synthesis, Ural Division of RAS, 620990, 22/20 S. Kovalevskoy st./Akademicheskaya st., Yekaterinburg, Russian Federation.
Ural Federal University Named After the First President of Russia B. N. Yeltsin, Department of Analytical Chemistry, 620002, 19 Mira St., Yekaterinburg, Russian Federation.
Bioorg Med Chem Lett. 2020 Jul 1;30(13):127216. doi: 10.1016/j.bmcl.2020.127216. Epub 2020 Apr 27.
Stable σ-adducts of azolo[5,1-c]triazines and azolo[1,5-a]pyrimidines with different polyphenols were synthesized and their antioxidant and antiviral activity were investigated. Their affinity to viral hemagglutinin was assessed using molecular modelling. The phloroglucinol-modified azolo-azines possessed the highest virus-inhibiting activity. According to the results of the study of antioxidant properties of compounds, the most promising ones exhibiting highest antioxidant capacity were adducts containing in their structure pyrogallol and catechol residues and 6-nitro-triazolotriazin-7-ol scaffold. No correlation between antioxidant and virus-inhibiting activity of compounds studied was detected. The most active compounds demonstrated the ability to prevent binding of viral hemagglutinin with cellular receptor as shown in hemagglutination inhibition assay. Our results demonstrate that polyphenol-modified azolo-azines are prospective for further optimization as potential antivirals and that their action is directed against viral hemagglutinin.
稳定的 σ-加合物的唑并[5,1-c]三嗪和唑并[1,5-a]嘧啶与不同的多酚被合成和研究其抗氧化和抗病毒活性。使用分子模拟评估了它们与病毒血凝素的亲和力。间苯三酚修饰的唑并杂环具有最高的病毒抑制活性。根据化合物抗氧化性质的研究结果，表现出最高抗氧化能力的最有前途的化合物含有在其结构中的焦儿茶酚和邻苯二酚残基和 6-硝基三唑并三嗪-7-醇支架。在研究的化合物中，没有检测到抗氧化和病毒抑制活性之间的相关性。在血凝抑制试验中，最活跃的化合物表现出阻止病毒血凝素与细胞受体结合的能力。我们的结果表明，多酚修饰的唑并杂环是进一步优化作为潜在抗病毒药物的有希望的候选物，它们的作用是针对病毒血凝素。
