Department of Fine Organic Synthesis and Chemistry of Dyes, D.I. Mendeleev University of Chemical Technology of Russia, Miusskaya sq., 9, Moscow, 125047, Russia.
A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilova str., 28, Moscow, 119991, Russia.
Med Chem. 2023;19(5):468-477. doi: 10.2174/1573406419666221125101053.
In 1980, smallpox became the first viral disease eradicated through vaccination. After the termination of the Smallpox Eradication Program, the global immunization of the population also ceased. Now, most people do not have any immunity against infections caused by orthopoxviruses. Emerging cases of zoonotic orthopox infections transferring to humans inspire the search for new small organic molecules possessing antiviral activity against orthopoxviruses.
Here, we present the synthesis and evaluation of antiviral activity against one of the orthopoxviruses, i.e., Vaccinia virus, of hybrid structures containing 1-hydroxyimidazole and benzopyranone moieties.
Novel 2-(3-coumarinyl)-1-hydroxyimidazoles were synthesized. Their prototropic tautomerism was considered using H NMR spectroscopy. Antiviral activity of both new 2-(3-coumarinyl)- 1-hydroxyimidazoles and previously described 2-(3-chromenyl)-1-hydroxyimidazoles against Vaccinia virus was evaluated in Vero cell culture.
Newly synthesized 2-(3-coumarinyl)-1-hydroxyimidazoles existed in CDCl as a mixture of prototropic tautomers (N-hydroxyimidazole and imidazole N-oxide), transition to DMSO-d6 resulting in the prevalence of N-oxide tautomer. Evaluation of cytotoxicity and antiviral activity against Vaccinia virus was performed in Vero cell culture. Compounds possessing high antiviral activity were present in both series. It was demonstrated that the structure of heterocyclic substituent in position 2 of imidazole impacted the cytotoxicity of substances under consideration. Thus, molecules containing coumarin moiety exhibited lower toxicity than similarly substituted 2-(3-chromenyl)-1- hydroxyimidazoles.
Perspective virus inhibiting compounds possessing antiviral activity against Vaccinia virus were revealed in the series of 2-(3-coumarinyl)-1-hydroxyimidazoles.
1980 年，天花成为第一种通过疫苗接种根除的病毒病。在消灭天花计划终止后，全球人口的免疫接种也停止了。现在，大多数人对正痘病毒引起的感染没有任何免疫力。人畜共患正痘感染的新发病例转移到人类身上，激发了人们对具有抗正痘病毒活性的新型小分子有机化合物的研究。
本研究介绍了含有 1-羟基咪唑和苯并吡喃酮部分的杂合结构物针对一种正痘病毒，即痘苗病毒的合成与抗病毒活性评价。
合成了新型 2-(3-香豆酰基)-1-羟基咪唑。利用 H NMR 光谱研究了它们的质子互变异构。在 Vero 细胞培养中评价了两种新型 2-(3-香豆酰基)-1-羟基咪唑和以前描述的 2-(3-色烯基)-1-羟基咪唑对痘苗病毒的抗病毒活性。
新合成的 2-(3-香豆酰基)-1-羟基咪唑在 CDCl3 中以质子互变异构体（N-羟基咪唑和咪唑 N-氧化物）的混合物形式存在，转变为 DMSO-d6 导致 N-氧化物互变异构体占优势。在 Vero 细胞培养中进行了细胞毒性和抗痘苗病毒活性评价。两个系列中都存在具有高抗病毒活性的化合物。结果表明，咪唑 2 位杂环取代基的结构影响了所研究物质的细胞毒性。因此，含有香豆素部分的分子比具有相似取代基的 2-(3-色烯基)-1-羟基咪唑毒性更低。
在 2-(3-香豆酰基)-1-羟基咪唑系列中发现了具有抗痘苗病毒活性的有前景的病毒抑制化合物。
