Anti-influenza activity of diazaadamantanes combined with monoterpene moieties. / Suslov, Evgeniy; Zarubaev, Vladimir V.; Slita, Alexander V. et al.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 27, No. 19, 01.10.2017, p. 4531-4535.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Anti-influenza activity of diazaadamantanes combined with monoterpene moieties
AU - Suslov, Evgeniy
AU - Zarubaev, Vladimir V.
AU - Slita, Alexander V.
AU - Ponomarev, Konstantin
AU - Korchagina, Dina
AU - Ayine-Tora, Daniel M.
AU - Reynisson, Jóhannes
AU - Volcho, Konstantin
AU - Salakhutdinov, Nariman
N1 - Publisher Copyright: © 2017 Elsevier Ltd
PY - 2017/10/1
Y1 - 2017/10/1
N2 - 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).
AB - 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).
KW - Antivirals
KW - Citronellal
KW - Diaza-adamantane
KW - Influenza
KW - Myrtenal
KW - Terpene
KW - Antiviral Agents/chemical synthesis
KW - Structure-Activity Relationship
KW - Aza Compounds/chemistry
KW - Dose-Response Relationship, Drug
KW - Microbial Sensitivity Tests
KW - Influenza A Virus, H1N1 Subtype/drug effects
KW - Adamantane/chemistry
KW - Monoterpenes/chemistry
KW - Molecular Structure
KW - EMPIRICAL SCORING FUNCTIONS
KW - DATA-BANK
KW - DUAL INHIBITORS
KW - WILD-TYPE
KW - M2 PROTON CHANNEL
KW - INFLUENZA-A VIRUS
KW - PROTEIN-LIGAND DOCKING
KW - ADAMANTANE DERIVATIVES
KW - ANTIVIRAL ACTIVITY
KW - M-2 ION-CHANNEL
UR - http://www.scopus.com/inward/record.url?scp=85028690947&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2017.08.062
DO - 10.1016/j.bmcl.2017.08.062
M3 - Article
C2 - 28886889
AN - SCOPUS:85028690947
VL - 27
SP - 4531
EP - 4535
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 19
ER -
ID: 8969281