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

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

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere1900340
JournalChemistry and Biodiversity
Volume16
Issue number11
DOIs
Publication statusPublished - 29 Oct 2019

Keywords

  • (+)-camphor
  • (−)-cytisine
  • 1,2,3-triazoles
  • azides
  • camphecene
  • cytotoxicity
  • heterocyclization
  • terpenoids
  • ‘click’ chemistry
  • DESIGN
  • HEMAGGLUTININ
  • BORNEOL DERIVATIVES
  • 'click' chemistry
  • 1
  • 2
  • IN-VITRO
  • (-)-cytisine
  • 3-triazoles
  • (-)-CYTISINE
  • INFLUENZA-VIRUS
  • INHIBITORS
  • BINDING
  • LEAD

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