Design, synthesis and biological evaluation of substituted flavones and aurones as potential anti-influenza agents

  • Bioorg Med Chem. 2020 Jan 1;28(1):115191. doi: 10.1016/j.bmc.2019.115191.
Anand S Chintakrindi  1 ,  Devanshi J Gohil  2 ,  Abhay S Chowdhary  2 ,  Meena A Kanyalkar  3
Affiliations
  • 1. Department of Pharmaceutical Chemistry, Prin. K.M. Kundnani College of Pharmacy, Cuffe Parade, Mumbai 400005, India.
  • 2. Department of Virology, Haffkine Institute for Training, Research and Testing, Parel, Mumbai 400012, India.
  • 3. Department of Pharmaceutical Chemistry, Prin. K.M. Kundnani College of Pharmacy, Cuffe Parade, Mumbai 400005, India. Electronic address: [email protected].
PMID: 31744778 DOI: 10.1016/j.bmc.2019.115191
Abstract

We designed a series of substituted Flavones and aurones as non-competitive H1N1 neuraminidase (NA) inhibitors and anti-influenza agents. The molecular docking studies showed that the designed Flavones and aurones occupied 150-cavity and 430-cavity of H1N1-NA. We then synthesized these compounds and evaluated these for cytotoxicity, reduction in H1N1 virus yield, H1N1-NA inhibition and kinetics of inhibition. The virus yield reduction assay and H1N1-NA inhibition assay demonstrated that the compound 1f (4-methoxyflavone) had the lowest EC50 of 9.36 nM and IC50 of 8.74 μM respectively. Moreover, kinetic studies illustrated that compounds 1f and 2f had non-competitive inhibition mechanism.

Keywords
Aurones; Flavone; H1N1; Influenza; Neuraminidase; Non-competitive.