Anti-viral activity of (-)- and (+)-usnic acids and their derivatives against influenza virus A(H1N1)2009

Anti-viral activity of (-)- and (+)-usnic acids and their derivatives against influenza virus A(H1N1)2009 Научная публикация

Журнал

Bioorganic and Medicinal Chemistry Letters
ISSN: 0960-894X , E-ISSN: 1464-3405

Вых. Данные

Год: 2012, Том: 22, Номер: 23, Страницы: 7060-7064 Страниц : DOI: 10.1016/j.bmcl.2012.09.084

Ключевые слова

Usnic acid; Enantiomer; Influenza; Pandemic; Antiviral

Авторы

Sokolov Dmitriy N. ² , Zarubaev Vladimir V. ¹ , Shtro Anna A. ¹ , Polovinka Marina P. ² , Luzina Olga A. ² , Komarova Nina I. ² , Salakhutdinov Nariman F. ² , Kiselev Oleg I. ¹

Организации

1	(Данные Web of science) Influenza Res Inst, Dept Chemotherapy, St Petersburg 197376, Russia
2	(Данные Web of science) Russian Acad Sci, Siberian Branch, Novosibirsk Organ Chem Inst, Novosibirsk 630090, Russia

Influenza is a widespread respiratory infection. Every year it causes epidemics, quickly spreading from country to country, or even pandemics, involving a significant part of the human population of the earth. Being a highly variable infection, influenza easy accumulates the resistance mutations to many antivirals. Usnic acid, a dibenzofuran originally isolated from lichens belongs to the secondary metabolites and has a broad spectrum of biological activity. In humans, it can act as an anti-inflammatory, antimitotic, antineoplasic, antibacterial, and antimycotic agent. In this work we studied for the first time the antiviral activity of usnic acid and its derivatives against the pandemic influenza virus A(H1N1)pdm09. A total of 26 compounds representing (+) and (-) isomers of usnic acid and their derivates were tested for cytotoxicity and anti-viral activity in MDCK cells by microtetrazolium test and virus yield assay, respectively. Based on the results obtained, 50% cytotoxic dose (CTD50) and 50% effective dose (ED50) and selectivity index (SI) were calculated for each compound. Eleven of them were found to have SI higher than 10 (highest value 37.3). Absolute configuration was shown to have critical significance for the anti-viral activity. With minor exceptions, in the pair of enantiomers, (-)-usnic acid was more active comparing to (+)-isomer, but its biological activity was reversed after the usnic acid was chemically modified. Based on the obtained results, derivatives of usnic acid should be considered as prospective compounds for further optimization as anti-influenza substances. (C) 2012 Elsevier Ltd. All rights reserved.

Sokolov D.N. , Zarubaev V.V. , Shtro A.A. , Polovinka M.P. , Luzina O.A. , Komarova N.I. , Salakhutdinov N.F. , Kiselev O.I.
Anti-viral activity of (-)- and (+)-usnic acids and their derivatives against influenza virus A(H1N1)2009
Bioorganic and Medicinal Chemistry Letters. 2012. V.22. N23. P.7060-7064. DOI: 10.1016/j.bmcl.2012.09.084 WOS Scopus РИНЦ

Опубликована в печати:

1 дек. 2012 г.

Web of science	WOS:000310583100013
Scopus	2-s2.0-84869080640
РИНЦ	20491665
OpenAlex	W1973671680