Synthesis of d-(+)-camphor-based N-acylhydrazones and their antiviral activity

  • Medchemcomm. 2018 Oct 26;9(12):2072-2082. doi: 10.1039/c8md00442k.
Kseniya S Kovaleva  1  2  3 ,  Fedor I Zubkov  3 ,  Nikolay I Bormotov  4 ,  Roman A Novikov  5 ,  Pavel V Dorovatovskii  6 ,  Victor N Khrustalev  3  6 ,  Yuriy V Gatilov  1  2 ,  Vladimir V Zarubaev  7 ,  Olga I Yarovaya  1  2 ,  Larisa N Shishkina  4 ,  Nariman F Salakhutdinov  1  2
Affiliations
  • 1. Novosibirsk Institute of Organic Chemistry , Siberian Branch of the Russian Academy of Sciences , Lavrentjev Ave. 9 , 630090 Novosibirsk , Russian Federation . Email: [email protected].
  • 2. Novosibirsk State University , Pirogova St. 2 , 630090 Novosibirsk , Russian Federation . Email: [email protected].
  • 3. RUDN University , 6 Miklukho-Maklaya St , 117198 Moscow , Russian Federation . Email: [email protected].
  • 4. Department of Prevention and Treatment of Especially Dangerous Infections , State Research Centre of Virology and Biotechnology VECTOR , Koltsovo , Novosibirsk Region , 630559 , Russian Federation.
  • 5. Engelhardt Institute of Molecular Biology , Russian Academy of Sciences , 32 Vavilov St. , 119991 Moscow , Russian Federation.
  • 6. National Research Center "Kurchatov Institute" , 1 Acad. Kurchatov Sq. , 123182 Moscow , Russian Federation.
  • 7. Pasteur Institute of Epidemiology and Microbiology , 14 Mira str. , 197101 St. Petersburg , Russia.
PMID: 30746065 DOI: 10.1039/c8md00442k
Abstract

The design and synthesis of a series of novel d-(+)-camphor N-acylhydrazones exhibiting inhibitory activity against vaccinia and influenza viruses are presented. An easy pathway to camphor-based N-acylhydrazones containing in their structure aliphatic, aromatic, and heterocyclic pharmacophore scaffolds has been developed. The conformation and configuration of the synthesized hydrazones were thoroughly characterized by a complete set of spectral characterization techniques, including 2D NMR spectroscopy, mass spectrometry, and X-ray diffraction analysis. In vitro screening for activity against vaccinia virus (VV) and influenza H1N1 virus was carried out for the obtained compounds. It was revealed that the derived N-acylhydrazones exhibited significant Antiviral activity with a selectivity index >280 against VV for the most promising compound.