Simplistic perylene-related compounds as inhibitors of tick-borne encephalitis virus reproduction. Issue 10 (15th May 2020)

• Record Type: Journal Article
• Authors: Slesarchuk, Nikita A.; Khvatov, Evgeny V.; Chistov, Alexey A.; Proskurin, Gleb V.; Nikitin, Timofei D.; Lazarevich, Anastasiya I.; Ulanovskaya, Angelina A.; Ulashchik, Egor A.; Orlov, Alexey A.; Jegorov, Artjom V.; Ustinov, Alexey V.; Tyurin, Anton P.; Shmanai, Vadim V.; Ishmukhametov, Aydar A.; Korshun, Vladimir A.; Osolodkin, Dmitry I.; Kozlovskaya, Liubov I.; Aralov, Andrey V.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 30:Issue 10(2020)
• Publication Date: 2020-05-15
• Subjects: RAFI -- Antiviral activity -- Tick-borne encephalitis virus -- Antivirals -- Heliomycin; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2020.127100
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Rigid amphipathic fusion inhibitors are potent broad-spectrum antivirals based on the perylene scaffold, usually decorated with a hydrophilic group linked via ethynyl or triazole. We have sequentially simplified these structures by removing sugar moiety, then converting uridine to aniline, then moving to perylenylthiophenecarboxylic acids and to perylenylcarboxylic acid. All these polyaromatic compounds, as well as antibiotic heliomycin, still showed pronounced activity against tick-borne encephalitis virus (TBEV) with limited toxicity in porcine embryo kidney (PEK) cell line. 5-(Perylen-3-yl)-2-thiophenecarboxylic acid (5a ) showed the highest antiviral activity with 50% effective concentration of approx. 1.6 nM.