SARS-CoV 3CLpro inhibitory effects of quinone-methide triterpenes from Tripterygium regelii

Bioorg Med Chem Lett. 2010 Mar 15;20(6):1873-6. doi: 10.1016/j.bmcl.2010.01.152. Epub 2010 Feb 4.

Abstract

Quinone-methide triterpenes, celastrol (1), pristimerin (2), tingenone (3), and iguesterin (4) were isolated from Triterygium regelii and dihydrocelastrol (5) was synthesized by hydrogenation under palladium catalyst. Isolated quinone-methide triterpenes (1-4) and 5 were evaluated for SARS-CoV 3CL(pro) inhibitory activities and showed potent inhibitory activities with IC(50) values of 10.3, 5.5, 9.9, and 2.6 microM, respectively, whereas the corresponding 5 having phenol moiety was observed in low activity (IC(50)=21.7 microM). As a result, quinone-methide moiety in A-ring and more hydrophobic E-ring assist to exhibit potent activity. Also, all quinone-methide triterpenes 1-4 have proven to be competitive by the kinetic analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology*
  • Benzoquinones / chemistry*
  • Models, Molecular
  • Plant Extracts / pharmacology*
  • Severe acute respiratory syndrome-related coronavirus / drug effects*
  • Tripterygium / chemistry*
  • Triterpenes / chemistry
  • Triterpenes / pharmacology*

Substances

  • Antiviral Agents
  • Benzoquinones
  • Plant Extracts
  • Triterpenes
  • quinone