Novel daidzein analogs and their in vitro anti-influenza activities

Chem Biodivers. 2015 Apr;12(4):685-96. doi: 10.1002/cbdv.201400337.

Abstract

A series of novel isoflavonoids were synthesized based on structural modifications of daidzein, an active ingredient of traditional Chinese medicine (TCM) and evaluated for their anti-influenza activity, in vitro, against H1N1 Tamiflu-resistant (H1N1 TR) virus in the MDCK cell line. Among them, 4-oxo-4H-1-benzopyran-8-carbaldehydes 11a-11g were most promising, and they demonstrated better activities and selectivities comparable to those the reference ribarivin, a nucleoside antiviral agent. 3-(4-Bromophenyl)-7-hydroxy-4-oxo-4H-1-benzopyran-8-carboxaldehyde (11c) displayed the best inhibitory activity (EC50 , 29.0 μM) and selectivity index (SI>10.3). Analysis of the structureactivity relationships (SAR) indicated that both the non-naturally-occurring Br-substituted B-ring and appropriate CHO and OH groups on the A-ring might be critical for the activity and selectivity against H1N1 TR influenza viruses.

Keywords: Anti-influenza virus; Daidzein; H1N1 Tamiflu-resistant virus; Isoflavonoids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Chemistry Techniques, Synthetic
  • Dogs
  • Drug Evaluation, Preclinical / methods
  • Drug Resistance, Viral / drug effects
  • Influenza A Virus, H1N1 Subtype / drug effects*
  • Isoflavones / chemical synthesis
  • Isoflavones / chemistry*
  • Isoflavones / pharmacology*
  • Madin Darby Canine Kidney Cells / drug effects
  • Madin Darby Canine Kidney Cells / virology
  • Molecular Structure
  • Oseltamivir / pharmacology
  • Ribavirin / pharmacology
  • Structure-Activity Relationship

Substances

  • Antiviral Agents
  • Isoflavones
  • Oseltamivir
  • Ribavirin
  • daidzein