Anti-influenza activity of diazaadamantanes combined with monoterpene moieties

Suslov, Evgeniy; Zarubaev, Vladimir V.; Slita, Alexander V.; Ponomarev, Konstantin; Korchagina, Dina; Ayine-Tora, Daniel M.; Reynisson, Jóhannes; Volcho, Konstantin; Salakhutdinov, Nariman

Abstract

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 citronellal 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).

Citation

Suslov, E., Zarubaev, V. V., Slita, A. V., Ponomarev, K., Korchagina, D., Ayine-Tora, D. M., …Salakhutdinov, N. (2017). Anti-influenza activity of diazaadamantanes combined with monoterpene moieties. Bioorganic and Medicinal Chemistry Letters, 27(19), 4531-4535. https://doi.org/10.1016/j.bmcl.2017.08.062

• Journal Article Type: Article
• Acceptance Date: Aug 29, 2017
• Online Publication Date: Sep 1, 2017
• Publication Date: 2017-10
• Deposit Date: Jun 8, 2023
• Journal: Bioorganic & Medicinal Chemistry Letters
• Print ISSN: 0960-894X
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 27
• Issue: 19
• Pages: 4531-4535
• DOI: https://doi.org/10.1016/j.bmcl.2017.08.062
• Keywords: Organic Chemistry; Clinical Biochemistry; Drug Discovery; Pharmaceutical Science; Molecular Biology; Molecular Medicine; Biochemistry
• Additional Information: This article is maintained by: Elsevier; Article Title: Anti-influenza activity of diazaadamantanes combined with monoterpene moieties; Journal Title: Bioorganic & Medicinal Chemistry Letters; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.bmcl.2017.08.062; Content Type: article; Copyright: © 2017 Elsevier Ltd. All rights reserved.