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. Setzer1,*, 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
Further Information

Publication History

Publication Date:
31 December 2001 (online)

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.

References

  • 1 The Wealth of India Raw Materials, Vol. 9.. Publications and Informations Directorate,. CSIR, New Delhi; 1948 - 1976
  • 2 Pillai  N R,, Seshadri  C,, Santhakumari  G.. Hypoglycaemic activity of the root bark of Salacia prenoides. .  Indian Journal of Experimental Biology. 1979;;  17 1279-80
  • 3 Viswanathan  N I.. Salaspermic acid, a new triterpene acid from Salacia macrosperma Wight.  Journal of the Chemical Society, Perkin Transactions I. 1979;;  349-52
  • 4 Tewari  N C,, Ayengar  K N,, Rangaswami  S.. Triterpenes of the root-bark of Salacia prenoides DC.  Journal of the Chemical Society, Perkin Transactions I. 1974;;  146-52
  • 5 Sneden  A T.. Isoiguesterin, a new antileukemic bisnortriterpene from Salacia madagascariensis. .  Journal of Natural Products. 1981;;  44 503-7
  • 6 Hisham  A,, Jaya Kumar  G J,, Fujimoto  Y,, Hara  N.. Salacianone and salacianol, two triterpenes from Salacia beddomei. .  Phytochemistry. 1995;;  40 1227-31
  • 7 Kawazoe  K,, Shimogai  N,, Takaishi  Y,, Rao  K S,, Imakura  Y.. Four stilbenes from Salacia lehmbachii. .  Phytochemistry. 1997;;  44 1569-73
  • 8 Figueiredo  J N,, Raz  B,, Sequin  U.. Novel quinone methides from Salacia kraussii with in vitro antimalarial activity.  Journal of Natural Products. 1998;;  61 718-23
  • 9 Setzer  W N,, Setzer  M C,, Hopper  A L,, Moriarity  D M,, Lehrman  G K,, Niekamp  K L,, Morcomb  S M,, Bates  R B,, McClure  K J,, Stessman  C C,, Haber  W A.. The cytotoxic activity of a Salacia liana species from Monteverde, Costa Rica, is due to a high concentration of tingenone.  Planta Medica. 1998;;  64 583
  • 10 Haber  W A,, Zuchowski  W,, Bello  E.. An introduction to cloud forest trees: Monteverde, Costa Rica,.  La Nacion, San Jose, Costa Rica; 1996
  • 11 Knowles  B B,, Howe  C C,, Aden  D P.. Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen.  Science. 1980;;  209 497-9
  • 12 Cailleau  R,, Young  R,, Olive  M,, Reeves  W J.. Breast tumor cell lines from pleural effusions.  Journal of the National Cancer Institute. 1974;;  53 661-74
  • 13 Klass  J,, Tinto  W F,, McLean  S,, Reynolds  W F.. Friedelane triterpenoids from Peritassa compta: complete 1H and 13C assignments by 2D NMR spectroscopy.  Journal of Natural Products. 1992;;  55 1626-30
  • 14 Betancor  C,, Freire  R,, Gonzalez  A G,, Salazar  J A,, Pascard  C,, Prange  T.. Three triterpenes and other terpenoids from Catha cassinoides. .  Phytochemistry. 1980;;  19 1989-93
  • 15 Brown  P M,, Moir  M,, Thompson  R H,, King  T J,, Krishnamoorthy  V,, Seshadri  T R.. Tingenone and hydroxytingenone, triterpenoid quinone methides from Euonymus tingens. .  Journal of the Chemical Society, Perkin Transactions I. 1973;;  2721-5
  • 16 Gonzalez  A G,, Bazzochhi  I L,, Ravelo  A G,, Luis  J G,, Dominguez  X A,, Vazquez  G,, Cano  G.. Triterpenos y triterpenoquinonas de Rzedowskia tolantonguensis (Celastraceae).  Revista de Latinoamerica Quimica. 1987;;  18 83-8
  • 17 Alvarenga  N L,, Velazquez  C A,, Gomez  R,, Canela  N J,, Bazzocchi  I L,, Ferro  E A.. A new antibiotic nortriterpene quinone methide from Maytenus catingarum. .  Journal of Natural Products. 1999;;  62 750-1
  • 18 Ngassapa  O,, Soejarto  D D,, Pezzuto  J M,, Farnsworth  N R.. Quinone-methide triterpenes and salaspermic acid from Kokoona ochracea. .  Journal of Natural Products. 1994;;  57 1-8
  • 19 Goijman  S G,, Turrens  J F,, Barini-Bettolo  G B,, Stoppani  A O.. Effect of tingenone, a quinonoid triterpene, on growth and macromolecule biosynthesis in Trypanosoma cruzi. .  Experientia. 1985;;  41 646-8
  • 20 Campanelli  A R,, D'Alagni  M,, Marini-Bettolo  G B.. Spectroscopic evidence for the interaction of tingenone with DNA.  FEBS Letters. 1980;;  122 256-60
  • 21 Miller  K J,, Newlin  D D.. Interactions of molecules with nucleic acids. VI. Computer design of chromophoric intercalating agents.  Biopolymers. 1982;;  21 633-52
  • 22 Thompson  D C,, Thompson  J A,, Sugumaran  M,, Moldeus  P.. Biological and toxicological consequences of quinone methide formation.  Chemico-Biological Interactions. 1993;;  86 129-62
  • 23 Bolton  J L,, Comeau  E,, Vukomanovic  V.. The influence of 4-alkyl substituents on the formation and reactivity of 2-methoxy-quinone methides: evidence that extended pi-conjugation dramatically stabilizes the quinone methide formed from eugenol.  Chemico-Biological Interactions. 1995;;  95 279-90
  • 24 Bolton  J L,, Turnipseed  S B,, Thompson  J A.. Influence of quinone methide reactivity on the alkylation of thiol and amino groups in proteins: studies utilizing amino acid and peptide models.  Chemico-Biological Interactions. 1997;;  107 185-200
  • 25 Li  T,, Zeng  Q,, Rokita  S E.. Target-promoted alkylation of DNA.  Bioconjugate Chemistry. 1994;;  5 497-500
  • 26 Lewis  M A,, Yoerg  D G,, Bolton  J L,, Thompson  J A.. Alkylation of 2′-deoxynucleosides and DNA by quinone methides derived from 2,6-di-tert-butyl-4-methylphenol.  Chemical Research in Toxicology. 1996;;  9 1368-74
  • 27 Mayalarp  S P,, Hargreaves  R H,, Butler  J,, O'Hare  C C,, Hartley  J A.. Cross-linking and sequence specific alkylation of DNA by aziridinylquinones. 1. Quinone methides.  Journal of Medicinal Chemistry. 1996;;  39 531-7
  • 28 Bolton  J L,, Shen  L.. p-Quinone methides are the major decomposition products of catechol estrogen o-quinones.  Carcinogenesis. 1996;;  17 925-9
  • 29 Shen  L,, Qui  S,, Chen  Y,, Zhang  F,, van Breeman  R B,, Nikolic  D,, Bolton  J L.. Alkylation of 2′-deoxynucleosides and DNA by the Premarin metabolite 4-hydroxyequilenin semiquinone radical.  Chemical Research in Toxicology. 1998;;  11 94-101

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