Synthesis of Camphecene and Cytisine Conjugates Using Click Chemistry Methodology and Study of Their Antiviral Activity

Synthesis of Camphecene and Cytisine Conjugates Using Click Chemistry Methodology and Study of Their Antiviral Activity Full article

Journal

Chemistry and Biodiversity
ISSN: 1612-1872 , E-ISSN: 1612-1880

Output data

Year: 2019, Volume: 16, Number: 11, DOI: 10.1002/cbdv.201900340

Tags

azides; heterocyclization; (+)-camphor; (-)-cytisine; 'click' chemistry; terpenoids; 1; 2; 3-triazoles; camphecene; cytotoxicity

Authors

Artyushin Oleg.I. ¹ , Moiseeva Aleksandra A. ¹ , Zarubaev Vladimir V. ² , Slita Aleksander V. ² , Galochkina Anastasiya V. ² , Muryleva Anna A. ² , Borisevich Sophia S. ³ , Yarovaya Olga I. ^4,5 , Salakhutdinov Nariman F. ^4,5 , Brel Valery K. ¹

Affiliations

1	(Данные Web of science) Russian Acad Sci, AN Nesmeyanov Inst Organoelement Cpds, 28 Vavilova Str, Moscow 119991, Russia
2	(Данные Web of science) Paster Res Inst Epidemiol & Microbiol, 14 Mira Str, St Petersburg 197101, Russia
3	(Данные Web of science) RAS, Ufa Inst Chem UFRS, Octyabrya Av 71, Ufa 450078, Russia
4	(Данные Web of science) Russian Acad Sci, Siberian Branch, NN Vorozhtsov Novosibirsk Inst Organ Chem, Dept Med Chem, 9 Lavrentev Ave, Novosibirsk 630090, Russia
5	(Данные Web of science) Novosibirsk State Univ, 2 Pirogova Str, Novosibirsk 630090, Russia

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 mu mol, IC50=8 mu mol, 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.

Artyushin O.I. , Moiseeva A.A. , Zarubaev V.V. , Slita A.V. , Galochkina A.V. , Muryleva A.A. , Borisevich S.S. , Yarovaya O.I. , Salakhutdinov N.F. , Brel V.K.
Synthesis of Camphecene and Cytisine Conjugates Using Click Chemistry Methodology and Study of Their Antiviral Activity
Chemistry and Biodiversity. 2019. V.16. N11. DOI: 10.1002/cbdv.201900340 WOS Scopus РИНЦ

Published online:	Oct 29, 2019
Published print:	Nov 1, 2019

Web of science	WOS:000493015900001
Scopus	2-s2.0-85074762963
Elibrary	41697946
OpenAlex	W2981827462