Novel derivatives of usnic acid effectively inhibiting reproduction of influenza A virus

• Published in: Bioorganic & medicinal chemistry 2014-12, Vol.22 (24), p.6826-6836
• Main Authors: Shtro, Anna A., Zarubaev, Vladimir V., Luzina, Olga A., Sokolov, Dmitry N., Kiselev, Oleg I., Salakhutdinov, Nariman F.
• Format: Article
• Language: English
• Subjects: Animals; Anti-viral activity; Antiviral Agents - chemical synthesis; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Benzofurans - chemical synthesis; Benzofurans - chemistry; Benzofurans - pharmacology; Cell Survival - drug effects; Dogs; Humans; Influenza; Influenza A virus; Influenza A virus - physiology; Madin Darby Canine Kidney Cells; Stereoisomerism; Structure-Activity Relationship; Usnic acid; Usnic acid derivatives; Virus Replication - drug effects
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2014.10.033

[Display omitted] Influenza virus is serious human pathogen leading to high morbidity and mortality all over the world. Due to high rate of mutation, it is able to fast development of drug resistance that makes necessary to search novel antivirals with broad range and alternative targets. In the present study we describe synthesis and anti-viral activity of novel derivatives of usnic acid (2,6-diacetyl-7,9-dihydroxy-8,9b-dimethyl-1,3(2H,9bH)-dibenzo-furandione). It is shown that anti-viral activity of usnic acid can be increased by side moieties introduction. The modification with chalcones appeared to be the most effective. Our study revealed that (−)-usnic acid exhibited higher antiviral activity than its (+)-enantiomer, but in the pairs of enantiomer derivatives such as enamines, pyrazoles and chalcones, the (+)-enantiomers were more potent inhibitors of the virus. For other groups of compounds the inhibiting activities of the enantiomers were comparable. Further optimization of the structure could therefore result in development of novel anti-influenza compound with alternative target and mechanism of virus-inhibiting action.