Anti-influenza activity of diazaadamantanes combined with monoterpene moieties

作者:Suslov Evgeniy; Zarubaev Vladimir V*; Slita Alexander V; Ponomarev Konstantin; Korchagina Dina; Ayine Tora Daniel M; Reynisson Johannes; Volcho Konstantin; Salakhutdinov Nariman
来源:Bioorganic & Medicinal Chemistry Letters, 2017, 27(19): 4531-4535.
DOI:10.1016/j.bmcl.2017.08.062

摘要

The antiviral activity of several diaza-adamantanes containing monoterpenoid moieties against a rimantadine-resistant strain of the influenza A/Puerto Rico/8/34 (H1N1) virus was studied. Hetero-adamantanes containing monoterpene moieties at the aminal position of the heterocycle were found to exhibit lower activity compared to compounds with a diaza-adamantane fragment and a monoterpene moiety linked via an amino group at the 6-position of the hetero-adamantane ring. The highest selectivity index (a ratio of the 50% cytotoxic concentration to the 50% inhibitory concentration) out of 30 was observed for compound 8d, which contains a citronella] monoterpenoid moiety. Diaza-adamantane 8d was superior to its adamantane-containing analog 5 both in its anti-influenza activity and selectivity. Furthermore, 8d has more balanced physicochemical properties than 5, making the former a more promising drug candidate. Modelling these compounds against an influenza virus M2 ion channel predicted plausible binding modes to both the wild-type and the mutant (S31N).

  • 出版日期2017-10-1