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

William N. Setzer; Michael T. Holland; Carey A. Bozeman; Glenn F. Rozmus; Mary C. Setzer; Debra M. Moriarity; Sabine Reeb; Bernhard Vogler; Robert B. Bates; William A. Haber

doi:10.1055/s-2001-10879

Planta Medica, Table of Contents

Planta Med 2001; 67(1): 65-69
DOI: 10.1055/s-2001-10879

Original Paper

Georg Thieme Verlag Stuttgart · New York

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

William N. Setzer^1,*, Michael T. Holland¹ , Carey A. Bozeman¹ , Glenn F. Rozmus¹ , Mary C. Setzer² , Debra M. Moriarity² , Sabine Reeb³ , Bernhard Vogler³ , Robert B. Bates⁴ , William A. Haber⁵

¹ Department of Chemistry, University of Alabama in Huntsville, Huntsville, Alabama, U.S.A.
² Department of Biological Sciences, University of Alabama in Huntsville, Huntsville, Alabama, U.S.A.
³ Institut für Chemie, Universität Hohenheim, Stuttgart, Germany
⁴ Department of Chemistry, University of Arizona, Tucson, Arizona, U.S.A.
⁵ Missouri Botanical Garden, St. Louis, Missouri, U.S.A., Monteverde de Puntarenas, Costa Rica, Central America

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.

Key words

Salacia petenensis - Hippocrateaceae - cytotoxic - antibacterial - quinone methide - tingenone - netzahualcoyonol - molecular orbital - DNA

Full Text

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Professor William N. Setzer

Department of Chemistry

The University of Alabama in Huntsville

Huntsville

AL 35899

U.S.A.

Email: wsetzer@matsci.uah.edu

Phone: +1-256-824-6349