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DOI: 10.1055/s-2001-10879
Isolation and Frontier Molecular Orbital Investigation of Bioactive Quinone-Methide Triterpenoids from the Bark of Salacia petenensis
Publication History
Publication Date:
31 December 2001 (online)
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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
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