Synthesis and in vitro study of novel borneol derivatives as potent inhibitors of the influenza A virus

  • Medchemcomm. 2017 Mar 3;8(5):960-963. doi: 10.1039/c6md00657d.
A S Sokolova  1  2 ,  O I Yarovaya  1  2 ,  M D Semenova  1 ,  A A Shtro  3 ,  I R Orshanskaya  3 ,  V V Zarubaev  3 ,  N F Salakhutdinov  1  2
Affiliations
  • 1. Novosibirsk Institute of Organic Chemistry , Siberian Branch of the Russian Academy of Sciences , Lavrentjev Avenue 9 , 630090 Novosibirsk , Russia . Email: [email protected].
  • 2. Novosibirsk State University , Pirogova St. 2 , 630090 Novosibirsk , Russia.
  • 3. Laboratory of Chemotherapy , Influenza Research Institute , Prof. Popova St. 15/17 , 197376 St. Petersburg , Russia.
PMID: 30108810 DOI: 10.1039/c6md00657d
Abstract

Herein, we present the design and synthesis of a series of novel heterocyclic derivatives of (-)-borneol and (-)-isoborneol as potent inhibitors of the influenza A virus. All compounds were tested for their toxicity against MDCK cells and for virus-inhibiting activity against the Influenza Virus A/Puerto Rico/8/34 (H1N1). Compounds 7, 16 and 26 containing a morpholine fragment exhibited the highest efficiency as agents inhibiting the replication of the Influenza Virus A(H1N1) with selectivity indices of 82, 45 and 65, correspondingly. Derivatives 9 (SI = 23) and 18 (SI = 25) containing a 1-methylpiperazine motif showed moderate Antiviral activity. Structure-activity analysis of this new series of borneol derivatives revealed that a 1,7,7-trimethylbicyclo[2.2.1]heptan scaffold is required for the Antiviral activity.