tetano
Editor, Senior Moderator
Bioorg Med Chem Lett. 2017 Sep 1. pii: S0960-894X(17)30866-1. doi: 10.1016/j.bmcl.2017.08.062. [Epub ahead of print]
[h=1]Anti-influenza activity of diazaadamantanes combined with monoterpene moieties.[/h] Suslov E[SUP]1[/SUP], Zarubaev VV[SUP]2[/SUP], Slita AV[SUP]3[/SUP], Ponomarev K[SUP]1[/SUP], Korchagina D[SUP]1[/SUP], Ayine-Tora DM[SUP]4[/SUP], Reynisson J[SUP]4[/SUP], Volcho K[SUP]5[/SUP], Salakhutdinov N[SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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).
Copyright ? 2017. Published by Elsevier Ltd.
[h=4]KEYWORDS:[/h] Antivirals; Citronellal; Diaza-adamantane; Influenza; Myrtenal; Terpene
PMID: 28886889 DOI: 10.1016/j.bmcl.2017.08.062
[h=1]Anti-influenza activity of diazaadamantanes combined with monoterpene moieties.[/h] Suslov E[SUP]1[/SUP], Zarubaev VV[SUP]2[/SUP], Slita AV[SUP]3[/SUP], Ponomarev K[SUP]1[/SUP], Korchagina D[SUP]1[/SUP], Ayine-Tora DM[SUP]4[/SUP], Reynisson J[SUP]4[/SUP], Volcho K[SUP]5[/SUP], Salakhutdinov N[SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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).
Copyright ? 2017. Published by Elsevier Ltd.
[h=4]KEYWORDS:[/h] Antivirals; Citronellal; Diaza-adamantane; Influenza; Myrtenal; Terpene
PMID: 28886889 DOI: 10.1016/j.bmcl.2017.08.062