Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
Synthesis and structure-activity relationships of novel camphecene analogues as anti-influenza agents. / Yarovaya, Olga I.; Sokolova, Anastasiya S.; Mainagashev, Iliya Ya и др.
в: Bioorganic and Medicinal Chemistry Letters, Том 29, № 23, 126745, 01.12.2019.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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TY - JOUR
T1 - Synthesis and structure-activity relationships of novel camphecene analogues as anti-influenza agents
AU - Yarovaya, Olga I.
AU - Sokolova, Anastasiya S.
AU - Mainagashev, Iliya Ya
AU - Volobueva, Alexandrina S.
AU - Lantseva, Khristina
AU - Borisevich, Sophia S.
AU - Shtro, Anna A.
AU - Zarubaev, Vladimir V.
AU - Salakhutdinov, Nariman F.
N1 - Publisher Copyright: © 2019
PY - 2019/12/1
Y1 - 2019/12/1
N2 - A chemical library was constructed based on the scaffold of camphecene (2-(E)-((1R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene-aminoethanol). The modifications included introduction of mono-and bicyclic heterocyclic moieties in place of the terminal hydroxyl group of camphecene. All compounds were tested for cytotoxicity and anti-viral activity against influenza virus A/Puerto Rico/8/34 (H1N1) in MDCK cells. Among 15 tested compounds 11 demonstrated a selectivity index (SI) higher than 10 and IC50 values in the micromolar range. The antiviral activity and toxicity were shown to strongly depend on the nature of the heterocyclic substituent. Compounds 2 and 14 demonstrated the highest virus-inhibiting activity with SIs of 106 and 183, and bearing pyrrolidine and piperidine moieties, correspondingly. Compound 14 was shown to interfere with viral reproduction at early stages of the viral life cycle (0–2 h post-infection). Taken together, our data suggest potential of camphecene derivatives in particular and camphor-based imine derivatives in general as effective anti-influenza compounds.
AB - A chemical library was constructed based on the scaffold of camphecene (2-(E)-((1R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene-aminoethanol). The modifications included introduction of mono-and bicyclic heterocyclic moieties in place of the terminal hydroxyl group of camphecene. All compounds were tested for cytotoxicity and anti-viral activity against influenza virus A/Puerto Rico/8/34 (H1N1) in MDCK cells. Among 15 tested compounds 11 demonstrated a selectivity index (SI) higher than 10 and IC50 values in the micromolar range. The antiviral activity and toxicity were shown to strongly depend on the nature of the heterocyclic substituent. Compounds 2 and 14 demonstrated the highest virus-inhibiting activity with SIs of 106 and 183, and bearing pyrrolidine and piperidine moieties, correspondingly. Compound 14 was shown to interfere with viral reproduction at early stages of the viral life cycle (0–2 h post-infection). Taken together, our data suggest potential of camphecene derivatives in particular and camphor-based imine derivatives in general as effective anti-influenza compounds.
KW - Antivirals
KW - Camphecene
KW - Camphor
KW - Imine derivatives
KW - Influenza
KW - IN-VITRO
KW - INHIBITORS
KW - DERIVATIVES
KW - DISCOVERY
KW - VIRUSES
UR - http://www.scopus.com/inward/record.url?scp=85074404068&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2019.126745
DO - 10.1016/j.bmcl.2019.126745
M3 - Article
C2 - 31668423
AN - SCOPUS:85074404068
VL - 29
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 23
M1 - 126745
ER -
ID: 22087534