ABSTRACT
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.
Subject(s)
Antioxidants/pharmacology , Antiviral Agents/pharmacology , Polyphenols/pharmacology , Triazines/pharmacology , Triazoles/pharmacology , Animals , Antioxidants/chemical synthesis , Antioxidants/metabolism , Antiviral Agents/chemical synthesis , Antiviral Agents/metabolism , Dogs , Hemagglutinin Glycoproteins, Influenza Virus/metabolism , Influenza A virus/drug effects , Madin Darby Canine Kidney Cells , Microbial Sensitivity Tests , Molecular Docking Simulation , Polyphenols/chemical synthesis , Polyphenols/metabolism , Protein Binding , Triazines/chemical synthesis , Triazines/metabolism , Triazoles/chemical synthesis , Triazoles/metabolismABSTRACT
Influenza and ARVI represent the most numerous and dangerous group of causative agents of respiratory infections human. AIM: Characterization of the antiviral properties of enisamium iodide against human respiratory viruses in in vitro experiments. MATERIALS AND METHODS: In the course of experiments, the cytotoxic properties of enisamium iodide were studied against the cell lines Vero, MA-104, A549, L-41 and HEp-2. The antiviral activity of enisamium iodide was studied using virus yield reduction assay against influenza viruses, parainfluenza virus, respiratory syncytial virus, Coxsackie B3 and Coxsackie B4 viruses, as well as adenoviruses types 5 and 6. RESULTS: The most sensitive to the action of enisamium iodide was the human parainfluenza virus, whose activity decreased by 2.3 orders of magnitude under the action of the drug in A549 cells. Of the cell cultures used, enisamium iodide exhibited the maximum antiviral effect in human lung carcinoma cells A549, where, in its presence, the level of reproduction of adenoviruses of types 5 and 6, Coxsackie viruses B3 and B4, and human parainfluenza virus decreased by an order of magnitude or more. The antiviral activity of enisamium iodide was least manifested in Vero cells. CONCLUSION: According to the results of in vitro experiments, enisamium iodide can be considered as an antiviral drug with a wide spectrum of activity against human respiratory viruses.
