Synthesis of Camphecene and Cytisine Conjugates Using Click Chemistry Methodology and Study of Their Antiviral Activity. / Artyushin, Oleg I.; Moiseeva, Aleksandra A.; Zarubaev, Vladimir V. et al.
In: Chemistry and Biodiversity, Vol. 16, No. 11, e1900340, 29.10.2019.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Synthesis of Camphecene and Cytisine Conjugates Using Click Chemistry Methodology and Study of Their Antiviral Activity
AU - Artyushin, Oleg I.
AU - Moiseeva, Aleksandra A.
AU - Zarubaev, Vladimir V.
AU - Slita, Aleksander V.
AU - Galochkina, Anastasiya V.
AU - Muryleva, Anna A.
AU - Borisevich, Sophia S.
AU - Yarovaya, Olga I.
AU - Salakhutdinov, Nariman F.
AU - Brel, Valery K.
N1 - © 2019 Wiley-VHCA AG, Zurich, Switzerland.
PY - 2019/10/29
Y1 - 2019/10/29
N2 - A series of camphecene and quinolizidine alkaloid (−)-cytisine conjugates has been obtained for the first time using ‘click’ chemistry methodology. The cytotoxicity and virus-inhibiting activity of compounds were determined against MDCK cells and influenza virus A/Puerto Rico/8/34 (H1N1), correspondingly, in in vitro tests. Based on the results obtained, values of 50 % cytotoxic dose (CC50), 50 % inhibition dose (IC50) and selectivity index (SI) were determined for each compound. It has been shown that the antiviral activity is affected by the length and nature of linkers between cytisine and camphor units. Conjugate 13 ((1R,5S)-3-(6-{4-[(2-{(E)-[(1R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene]amino}ethoxy)methyl]-1H-1,2,3-triazol-1-yl}hexyl)-1,2,3,4,5,6-hexahydro-8H-1,5-methanopyrido[1,2-a][1,5]diazocin-8-one), which contains cytisine fragment separated from triazole ring by –C6H12– aliphatic linker, showed the highest activity at relatively low toxicity (CC50=168 μmol, IC50=8 μmol, SI=20). Its selectivity index appeared higher than that of reference compound, rimantadine. According to theoretical calculations, the antiviral activity of the lead compound 13 can be explained by its influence on the functioning of neuraminidase.
AB - A series of camphecene and quinolizidine alkaloid (−)-cytisine conjugates has been obtained for the first time using ‘click’ chemistry methodology. The cytotoxicity and virus-inhibiting activity of compounds were determined against MDCK cells and influenza virus A/Puerto Rico/8/34 (H1N1), correspondingly, in in vitro tests. Based on the results obtained, values of 50 % cytotoxic dose (CC50), 50 % inhibition dose (IC50) and selectivity index (SI) were determined for each compound. It has been shown that the antiviral activity is affected by the length and nature of linkers between cytisine and camphor units. Conjugate 13 ((1R,5S)-3-(6-{4-[(2-{(E)-[(1R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene]amino}ethoxy)methyl]-1H-1,2,3-triazol-1-yl}hexyl)-1,2,3,4,5,6-hexahydro-8H-1,5-methanopyrido[1,2-a][1,5]diazocin-8-one), which contains cytisine fragment separated from triazole ring by –C6H12– aliphatic linker, showed the highest activity at relatively low toxicity (CC50=168 μmol, IC50=8 μmol, SI=20). Its selectivity index appeared higher than that of reference compound, rimantadine. According to theoretical calculations, the antiviral activity of the lead compound 13 can be explained by its influence on the functioning of neuraminidase.
KW - (+)-camphor
KW - (−)-cytisine
KW - 1,2,3-triazoles
KW - azides
KW - camphecene
KW - cytotoxicity
KW - heterocyclization
KW - terpenoids
KW - ‘click’ chemistry
KW - DESIGN
KW - HEMAGGLUTININ
KW - BORNEOL DERIVATIVES
KW - 'click' chemistry
KW - 1
KW - 2
KW - IN-VITRO
KW - (-)-cytisine
KW - 3-triazoles
KW - (-)-CYTISINE
KW - INFLUENZA-VIRUS
KW - INHIBITORS
KW - BINDING
KW - LEAD
UR - http://www.scopus.com/inward/record.url?scp=85074762963&partnerID=8YFLogxK
U2 - 10.1002/cbdv.201900340
DO - 10.1002/cbdv.201900340
M3 - Article
C2 - 31647170
AN - SCOPUS:85074762963
VL - 16
JO - Chemistry and Biodiversity
JF - Chemistry and Biodiversity
SN - 1612-1872
IS - 11
M1 - e1900340
ER -
ID: 22321756