Isolation and Frontier Molecular Orbital Investigation of Bioactive Quinone-Methide Triterpenoids from the Bark of Salacia petenensis

Authors:
  • MHMichael T. Holland
    Michael T. Holland
  • CBCarey A. Bozeman
    Carey A. Bozeman
  • GRGlenn F. Rozmus
    Glenn F. Rozmus
  • MSMary C. Setzer
    Mary C. Setzer
  • DMDebra M. Moriarity
    Debra M. Moriarity
  • SRSabine Reeb
    Sabine Reeb
  • BVBernhard Vogler
    Bernhard Vogler
  • RBRobert B. Bates
    Robert B. Bates
  • WHWilliam A. Haber
    William A. Haber
Publisher website
Google Scholar
Abstract
The crude dichloromethane bark extract of Salacia petenensis (Hippocrateaceae) from Monteverde, Costa Rica, shows antibacterial and cytotoxic activity. Bioactivity-directed separation led to the isolation of tingenone and netzahualcoyonol as the biologically active materials. Also isolated from the extract were 3-methoxyfriedel-2-en-1-one (a new natural product) and 29-hydroxyfriedelan-3-one. The structures of these compounds were elucidated on the basis of NMR spectral analysis. Molecular orbital calculations have been carried out using the semi-empirical PM3 and Hartee-Fock 3-21G ab initio techniques on the quinone-methide nortriterpenoids tingenone and netzahualcoyonol, as well as on the nucleotide bases adenine, guanine, cytosine, and thymine. The molecular orbital calculations suggest that a possible mode of cytotoxic action of quinone-methide triterpenoids involves quasi-intercalative interaction of the compounds with DNA followed by nucleophilic addition of the DNA base to carbon-6 of the triterpenoid.