Synthesis and structure-activity relationships of novel camphecene analogues as anti-influenza agents

Olga I. Yarovaya, Anastasiya S. Sokolova, Iliya Ya Mainagashev, Alexandrina S. Volobueva, Khristina Lantseva, Sophia S. Borisevich, Anna A. Shtro, Vladimir V. Zarubaev, Nariman F. Salakhutdinov

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

A chemical library was constructed based on the scaffold of camphecene (2-(E)-((1R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene-aminoethanol). The modifications included introduction of mono-and bicyclic heterocyclic moieties in place of the terminal hydroxyl group of camphecene. All compounds were tested for cytotoxicity and anti-viral activity against influenza virus A/Puerto Rico/8/34 (H1N1) in MDCK cells. Among 15 tested compounds 11 demonstrated a selectivity index (SI) higher than 10 and IC50 values in the micromolar range. The antiviral activity and toxicity were shown to strongly depend on the nature of the heterocyclic substituent. Compounds 2 and 14 demonstrated the highest virus-inhibiting activity with SIs of 106 and 183, and bearing pyrrolidine and piperidine moieties, correspondingly. Compound 14 was shown to interfere with viral reproduction at early stages of the viral life cycle (0–2 h post-infection). Taken together, our data suggest potential of camphecene derivatives in particular and camphor-based imine derivatives in general as effective anti-influenza compounds.

Original languageEnglish
Article number126745
JournalBioorganic and Medicinal Chemistry Letters
Volume29
Issue number23
DOIs
Publication statusPublished - 1 Dec 2019

Keywords

  • Antivirals
  • Camphecene
  • Camphor
  • Imine derivatives
  • Influenza
  • IN-VITRO
  • INHIBITORS
  • DERIVATIVES
  • DISCOVERY
  • VIRUSES

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