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Planta Med 2008; 74(15): 1818-1822
DOI: 10.1055/s-0028-1088327
Original Paper
Natural Products Chemistry
© Georg Thieme Verlag KG Stuttgart · New York

Steroids, Alkaloids, and Coumarins from Gelsemium sempervirens

Zhizhen Zhang1 , Ping Wang1 , Wei Yuan1 , Shiyou Li1
  • 1National Center for Pharmaceutical Crops, Arthur Temple College of Forestry and Agriculture, Stephen F. Austin State University, Nacogdoches, Texas, USA
Further Information

Publication History

Received: April 18, 2008 Revised: August 21, 2008

Accepted: August 28, 2008

Publication Date:
17 November 2008 (online)

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Abstract

The 95 % ethanol extract of Gelsemium sempervirens showed inhibitory activity against human DNA topoisomerase I (Topo I). Phytochemical investigations of this active extract resulted in the isolation and identification of three new steroids (1 – 3), together with eight known compounds 12β-hydroxy-5α-pregn-16-ene-3,20-dione (4), gelsemine (5), sempervirine (6), scopoletin (7), 7-O-β-D-glucopyranosylscopoletin (8), 7-O-β-D-apiofuranosyl-(1→6)-β-D-glucopyranosylscopoletin (9), uvaol (10), and 2-(4-hydroxyphenyl)ethyl heptadecanoate (11). The structures of the new steroids were determined by extensive NMR and HR-ESI-MS analyses as 21-hydroxy-5α-pregn-16-ene-3,20-dione (1), 3-oxoandrosta-16-ene-17-carboxylic acid (2), and 3-oxoandrosta-4,16-diene-17-carboxylic acid (3). This study suggests that sempervirine (6) intercalates to DNA and also inhibits Topo I through modulating the enzyme activity with an IC50 of 54.5 ± 15.9 μM.

Key words

Gelsemium sempervirens - Loganiaceae - steroids, alkaloids - coumarins - human DNA topoisomerase I (topo I)

References

  • 1 Wyatt R, Broyles S B, Hamrick J L, Stoneburner A. Systematic relationships within Gelsemium (Loganiaceae): Evidence from isozymes and cladistics.  Syst Bot. 1993;  18 345-55
    CrossrefPubMedSearch in Google Scholar
  • 2 Kingsbury J M. Poisonous plants of the United States and Canada. Englewood Cliffs; Prentice-Hall, Inc 1964: 260
    Search in Google Scholar
  • 3 Takayama H, Sakai S. Gelsemium alkaloids. In: Cordell GA, editor The alkaloids. Vol 49 New York; Academic 1997: 1-78
    Search in Google Scholar
  • 4 Kitajima M, Urano A, Kogure N, Takayama H, Aimi N. New oxindole alkaloids and iridoid from Carolina jasmine (Gelsemium sempervirens Ait. f.).  Chem Pharm Bull. 2003;  51 1211-4
    CrossrefPubMedSearch in Google Scholar
  • 5 Kogure N, Nishiya C, Kitajima M, Takayama H. Six new indole alkaloids from Gelsemium sempervirens Ait. f.  Tetrahedron Lett. 2005;  46 5857-61
    CrossrefPubMedSearch in Google Scholar
  • 6 Kitajima M, Nakamura T, Kogure N, Ogawa M, Mitsuno Y, Ono K. et al . Isolation of gelsedine-type indole alkaloids from Gelsemium elegans and evaluation of the cytotoxic activity of Gelsemium alkaloids for A431 epidermoid carcinoma cells.  J Nat Prod. 2006;  69 715-8
    CrossrefPubMedSearch in Google Scholar
  • 7 Kogure N, Ishii N, Kitajima M, Wongseripipatana S, Takayama H. Four novel gelsenicine-related oxindole alkaloids from the leaves of Gelsemium elegans Benth.  Org Lett. 2006;  8 3085-8
    CrossrefPubMedSearch in Google Scholar
  • 8 Xu Y K, Yang S P, Liao S G, Zhang H, Lin L P, Ding J. et al . Alkaloids from Gelsemium elegans. .  J Nat Prod. 2006;  69 1347-50.
    CrossrefPubMedSearch in Google Scholar
  • 9 Rujjanawate C, Kanjanapothi D, Panthong A. Pharmacological effect and toxicity of alkaloids from Gelsemium elegans Benth.  J Ethnopharmacol. 2003;  89 91-5
    CrossrefPubMedSearch in Google Scholar
  • 10 Abdul Wahab K, Ahmad F B, Din L B, Swee Hung C, Shiueh Lian M. A study of the in vitro cytotoxic activity of Gelsemium elegans using human ovarian and breast cancer cell lines.  Trop Biomed. 2004;  21 139-44
    PubMedSearch in Google Scholar
  • 11 Beljanski M, Beljanski M S. Three alkaloids as selective destroyers of cancer cells in mice. Synergy with classic anticancer drugs.  Oncology. 1986;  43 198-203
    PubMedSearch in Google Scholar
  • 12 Beljanski M, Beljanski M S. Selective inhibition of in vitro synthesis of cancer DNA by alkaloids of β-carboline class.  Exp Cell Biol. 1982;  50 79-87
    PubMedSearch in Google Scholar
  • 13 Caprasse M, Houssier C. Physico-chemical investigation of the mode of binding of the alkaloids 5,6-dihydroflavopereirine and sempervirine with DNA.  Biochimie. 1984;  66 31-41
    CrossrefPubMedSearch in Google Scholar
  • 14 Sasiela C A, Stewart D H, Kitagaki J, Safiran Y J, Yang Y, Weissman A M. et al . Identification of inhibitors for MDM2 ubiquitin ligase activity from natural product extracts by a novel high-throughput electrochemiluminescent screen.  J Biomol Screen. 2008;  13 229-37
    CrossrefPubMedSearch in Google Scholar
  • 15 Schun Y, Cordell G A. 14β-Hydroxygelsedine, a new oxindole alkaloid from Gelsemium sempervirens. .  J Nat Prod. 1985;  48 788-91.
    CrossrefPubMedSearch in Google Scholar
  • 16 Schun Y, Cordell G A. Studies on the NMR spectroscopic properties of gelsemine – revisions and refinements.  J Nat Prod. 1985;  48 969-71.
    CrossrefPubMedSearch in Google Scholar
  • 17 Schun Y, Cordell G A. Cytotoxic steroids of Gelsemium sempervirens. .  J Nat Prod. 1987;  50 195-8.
    CrossrefPubMedSearch in Google Scholar
  • 18 Yuan W, Li S Y, Ownby S, Zhang Z Z, Wang P, Zhang W L. et al . Flavonoids, coumarins and triterpenes from the aerial parts of Cnidoscolus texanus. .  Planta Med. 2007;  73 1304-8
    Thieme ConnectPubMedSearch in Google Scholar
  • 19 Zhang Z Z, Li S Y. Cytotoxic triterpenoid saponins from the fruits of Aesculus pavia L.  Phytochemistry. 2007;  68 2075-86
    CrossrefPubMedSearch in Google Scholar
  • 20 Webb M R, Ebeler S E. A gel electrophoresis assay for the simultaneous determination of topoisomerase I inhibition and DNA intercalation.  Anal Biochem. 2003;  321 22-30
    CrossrefPubMedSearch in Google Scholar
  • 21 Hsiang Y H, Hertzberg R, Hecht S, Liu L F. Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I.  J Biol Chem. 1985;  260 14 873-8.
    PubMedSearch in Google Scholar
  • 22 Zhang Z Z, Li S Y, Zhang S, Liang C, Gorenstein D, Beasley R S. New camptothecin and ellagic acid analogues from the root bark of Camptotheca acuminata. .  Planta Med. 2004;  70 1216-21
    Thieme ConnectPubMedSearch in Google Scholar
  • 23 Blunt J W, Stothers J B. 13C n. m. r. spectra of steroids – a survey and commentary.  Org Magn Reson. 1977;  9 439-64
    CrossrefPubMedSearch in Google Scholar
  • 24 Gribble G W, Barden T C, Johnson D A. A directed metalation route to the zwitterionic indole alkaloids. Synthesis of sempervirine.  Tetrahedron. 1988;  44 3195-202
    CrossrefPubMedSearch in Google Scholar
  • 25 Zhang Z Z, Li S Y, Zhang S M. Six new triterpenoid saponins from the root and stem bark of Cephalanthus occidentalis L.  Planta Med. 2005;  71 355-61
    Thieme ConnectPubMedSearch in Google Scholar
  • 26 Mahato S B, Pundu A P. 13C NMR spectra of pentacyclic triterpenoids – a compilation and some salient features.  Phytochemistry. 1994;  37 1517-75.
    CrossrefPubMedSearch in Google Scholar
  • 27 Acevedo L, Martinez E, Castañeda P, Franzblau S, Timmermann B N, Linares E. et al . New phenylethanoids from Buddleja cordata subsp. cordata. .  Planta Med. 2000;  66 257- 61
    Thieme ConnectPubMedSearch in Google Scholar

Shiyou Li, PhD

National Center forPharmaceutical Crops

Arthur Temple College ofForestry and Agriculture

Stephen F. Austin StateUniversity

Nacogdoches

Texas 75962–6109

USA

Phone: +1-936-468-2071

Fax: +1-936-468-2489

Email: lis@sfasu.edu