Semisynthesis of (-)-Rutamarin Derivatives and Their Inhibitory Activity on Epstein-Barr Virus Lytic Replication

J Nat Prod. 2017 Jan 27;80(1):53-60. doi: 10.1021/acs.jnatprod.6b00415. Epub 2017 Jan 17.

Abstract

(+)-Rutamarin inhibits EBV lytic DNA replication with an IC50 of 7.0 μM. (-)-Chalepin, a (-)-rutamarin derivative, was isolated from the whole plant of Ruta graveolens and used as a precursor of (-)-rutamarin. Altogether, 28 (-)-rutamarin derivatives were synthesized starting from (-)-chalepin. Of these, 16 compounds (2a-e, 3b-e, 3g, 4f, 4k, 4m-p) were found to be more potent against EBV lytic DNA replication than (-)-chalepin. Compounds 4m, 4n, and 4p exhibited IC50 values of 1.5, 0.32, and 0.83 μM and showed selectivity index values (SI) of 801, 211, and >120, respectively. Thus, compounds 4m, 4n, and 4p are considered promising leads for further laboratory investigation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / isolation & purification*
  • Antiviral Agents / pharmacology*
  • Benzopyrans / chemical synthesis*
  • Benzopyrans / isolation & purification*
  • Benzopyrans / pharmacology*
  • DNA Replication / drug effects*
  • Furocoumarins / chemistry
  • Furocoumarins / isolation & purification*
  • Furocoumarins / pharmacology*
  • Herpesvirus 4, Human / drug effects*
  • Humans
  • Inhibitory Concentration 50
  • Molecular Structure
  • Ruta / chemistry*
  • Virus Replication / drug effects*

Substances

  • Antiviral Agents
  • Benzopyrans
  • Furocoumarins
  • chalepin
  • rutamarin