New class of hantaan virus inhibitors based on conjugation of the isoindole fragment to (+)-camphor or (−)-fenchone hydrazonesv

Olga I. Yarovaya, Kseniya S. Kovaleva, Anna A. Zaykovskaya, Liudmila N. Yashina, Nadezda S. Scherbakova, Dmitry N. Scherbakov, Sophia S. Borisevich, Fedor I. Zubkov, Alexandra S. Antonova, Roman Yu Peshkov, Ilia V. Eltsov, Oleg V. Pyankov, Rinat A. Maksyutov, Nariman F. Salakhutdinov

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1 Citation (Scopus)

Abstract

This work presents the design and synthesis of camphor, fenchone, and norcamphor N-acylhydrazone derivatives as a new class of inhibitors of the Hantaan virus, which causes haemorrhagic fever with renal syndrome (HFRS). A cytopathic model was developed for testing chemotherapeutics against the Hantaan virus, strain 76–118. In addition, a study of the antiviral activity was carried out using a pseudoviral system. It was found that the hit compound possesses significant activity (IC50 = 7.6 ± 2 µM) along with low toxicity (CC50 > 1000 µM). Using molecular docking procedures, the binding with Hantavirus nucleoprotein was evaluated and the correlation between the structure of the synthesised compounds and the antiviral activity was established.

Original languageEnglish
Article number127926
JournalBioorganic and Medicinal Chemistry Letters
Volume40
Early online date9 Mar 2021
DOIs
Publication statusPublished - 15 May 2021

Keywords

  • Antiviral
  • Hantavirus
  • HFRS
  • Isoindole
  • Terpene

OECD FOS+WOS

  • 1.04 CHEMICAL SCIENCES
  • 1.06 BIOLOGICAL SCIENCES

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