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Planta Med 2011; 77(17): 1905-1911
DOI: 10.1055/s-0031-1279984
Biological and Pharmacological Activity
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

Carlina Oxide – A Natural Polyacetylene from Carlina acaulis (Asteraceae) with Potent Antitrypanosomal and Antimicrobial Properties

Florian Herrmann1 , Razan Hamoud1 , Frank Sporer1 , Ahmed Tahrani1 , Michael Wink1
  • 1Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany
Further Information

Publication History

received March 3, 2011 revised May 19, 2011

accepted May 21, 2011

Publication Date:
15 June 2011 (online)

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Abstract

Carlina acaulis (Asteraceae) has a long history of medicinal use in Europe due to its antimicrobial properties. The strong activity of Carlina oxide, the main compound of the essential oil of C. acaulis against two MRSA strains, Streptococcus pyogenes, Pseudomonas aeruginosa, Candida albicans, and C. glabrata was confirmed. A strong and selective activity against Trypanosoma brucei brucei with an IC50 of 1.0 µg/mL and a SI of 446 compared to human HeLa cells was recorded. The selective toxicity of Carlina oxide makes it a promising lead compound for the development of drugs to treat African trypanosomiasis and multiresistant gram-positive bacteria.

Key words

Carlina acaulis - Asteraceae - Carlina oxide - Trypanosoma brucei brucei – MRSA - cytotoxicity

References

  • 1 Pink R, Hudson A, Mouriès M A, Bending M. Opportunities and challenges in antiparasitic drug discovery.  Nat Rev Drug Discov. 2005;  4 727-740
    CrossrefPubMedSearch in Google Scholar
  • 2 Trouiller P, Olliaro P, Torreele E, Orbinski J, Laing R, Ford N. Drug development for neglected diseases: a deficient market and a public-health policy failure.  Lancet. 2002;  359 2188-2194
    CrossrefPubMedSearch in Google Scholar
  • 3 Hoet S, Opperdoes F, Brun R, Quetin-Leclerq J. Natural products active against African trypanosomes: a step towards new drugs.  Nat Prod Rep. 2004;  21 353-364
    CrossrefPubMedSearch in Google Scholar
  • 4 Räz B, Iten M, Grether-Bühler Y, Kaminsky R, Brun R. The Alamar Blue assay to determine drug sensitivity of African trypanosomes (T. b. rhodesiense and T. b. gambiense) in vitro.  Acta Trop. 1997;  68 139-147
    CrossrefPubMedSearch in Google Scholar
  • 5 WHO report on global surveillance of epidemic-prone infectious diseases. World Health Organisation; 2000 WHO/CDS/CSR/ISR/2000.1. Available at http://www.who.int/csr/resources/publications/surveillance/en/a_tryps.pdf Accessed January 31, 2011
    Search in Google Scholar
  • 6 Barrett M P. The fall and rise of sleeping sickness.  Lancet. 1999;  353 1113-1114
    CrossrefPubMedSearch in Google Scholar
  • 7 Kristjanson P M, Swallow B M, Rowlands G J, Kruska R L, de Leeuw P N. Measuring the costs of African animal trypanosomiasis, the potential benefits of control and returns to research.  Agric Syst. 1999;  59 79-98
    CrossrefPubMedSearch in Google Scholar
  • 8 Fairlamb A H. Chemotherapy of human African trypanosomiasis: current status and future prospects.  Trends Parasitol. 2003;  19 488-494
    CrossrefPubMedSearch in Google Scholar
  • 9 Croft S L. The current status of antiparasitic chemotherapy.  Parasitology. 1997;  114 3-15
    PubMedSearch in Google Scholar
  • 10 Ross C A, Sutherland D V. Drug resistance in trypanosomatids. In: Hide G, Mottram J C, Coombs G H, Holmes P H, editors Trypanosomiasis and leishmaniasis: biology and control. Wallinford, Oxon: CAB International; 1997: 259-269
    Search in Google Scholar
  • 11 Newman D J, Cragg G M, Snader K M. Natural products as sources of new drugs over the period 1981–2002.  J Nat Prod. 2003;  66 1022-1037
    CrossrefPubMedSearch in Google Scholar
  • 12 Legros D, Ollivier G, Gastellu-Etchegorry M, Paquet C, Burri C, Jannin J, Büscher P. Treatment of human African trypanosomiasis–present situation and needs for research and development.  Lancet Infect Dis. 2002;  2 437-440
    CrossrefPubMedSearch in Google Scholar
  • 13 Brun R, Schumacher R, Schmid C, Kunz C, Burri C. The phenomenon of treatment failures in human African trypanosomiasis.  Trop Med Int Health. 2001;  6 906-914
    Search in Google Scholar
  • 14 Dordević S, Petrović S, Dobrić S, Milenković M, Vucićević D, Zizić S, Kukić J. Antimicrobial, anti-inflammatory, anti-ulcer and antioxidant activities of Carlina acanthifolia root essential oil.  J Ethnopharmacol. 2007;  109 458-463
    CrossrefPubMedSearch in Google Scholar
  • 15 van Wyk B E, Wink C, Wink M. Medicinal plants of the world. Pretoria, South Africa: Briza; 2004: 87
    Search in Google Scholar
  • 16 Wichtl M. Teedrogen und Phytopharmaka. Stuttgart, Germany: Wissenschaftliche Verlagsgesellschaft GmbH; 2002: 114-115
    Search in Google Scholar
  • 17 Djordjevic S, Petrovic S, Ristic M, Djokovic D. Composition of Carlina acanthifolia root essential oil.  Chem Nat Cmpd. 2005;  41 410-412
    PubMedSearch in Google Scholar
  • 18 Vitkova A, Evstatieva L. Plants rich in inulin from family Asteraceae. Godishnik na Sofiskiya Universitet “Sv. Kliment Okhridski”, Kniga 2.  Botanika. 2002;  92 107-111
    PubMedSearch in Google Scholar
  • 19 Chalchat J C, Dordević S, Gorunović M. Composition of the essential oil from the root of Carlina acaulis L. Asteraceae.  JEOR. 1996;  8 577-578
    PubMedSearch in Google Scholar
  • 20 Baltz T, Baltz D, Giroud C, Crockett J. Cultivation in a semi-defined medium of animal infective forms of Trypanosoma brucei, T. equiperdum, T. evansi, T. rhodesiense and T. gambiense.  EMBO J. 1985;  4 1273-1277
    PubMedSearch in Google Scholar
  • 21 Mosmann T. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays.  J Immunol Methods. 1983;  65 55-63
    CrossrefPubMedSearch in Google Scholar
  • 22 CLSI (Clinical and Laboratory Standards Institute) .Methods for antimicrobial susceptibility testing of anaerobic bacteria. In: Approved standards. 7th edition Wayne, Pennsylvania; 2007: M11-A7
    Search in Google Scholar
  • 23 Semmler F W. Zusammensetzung des aetherischen Oels der Eberwurzel (Carlina acaulis L.).  Chemiker Zeitung. 1889;  13 1158
    PubMedSearch in Google Scholar
  • 24 Gilman H, van Ess P R, Burtner R R. The constitution of Carlina oxide.  J Am Chem Soc. 1933;  55 3461-3463
    CrossrefPubMedSearch in Google Scholar
  • 25 Bohlmann F, Rode K M. Die Polyine der Gattung Carlina L.  Chem Ber. 1967;  100 1507-1514
    CrossrefPubMedSearch in Google Scholar
  • 26 Bohlmann F, von Kap-herr W. Polyacetylenverbindungen, XCII. Zur Biogenese des Carlinaoxyds.  Chem Ber. 1966;  99 148-150
    CrossrefPubMedSearch in Google Scholar
  • 27 Nair R, Vaghasiya Y, Chanda S. Antibacterial activity of Eucalpytus citriodora HK. oil on few clinically important bacteria.  AJB. 2007;  7 025-026
    PubMedSearch in Google Scholar
  • 28 Cosentino S, Tuberoso C L G, Pisano B, Satta M, Mascia V, Arzedi E, Palmas F. In-vitro antimicrobial activity and chemical composition of Sardinian Thymus essential oils.  Lett Appl Microbiol. 1999;  29 130-135
    CrossrefPubMedSearch in Google Scholar
  • 29 Krauth-Siegel R L, Bauer H, Schirmer R H. Dithiol proteins as guardians of the intracellular redox milieu in parasites: old and new targets in trypanosomes and malaria-causing plasmodia.  Angew Chem Int Ed Engl. 2005;  44 690-715
    CrossrefPubMedSearch in Google Scholar
  • 30 Fairlamb A H. Target discovery and validation with special reference to trypanothione. In: Fairlamb A H, Ridley R G, Vial H J, editors Drugs against parasitic diseases: R& D methodologies and issues. Geneva: WHO TDR; 2003: 107-118
    Search in Google Scholar
  • 31 Fairlamb A H, Blackburn P, Ulrich P, Chait B T, Cerami A. Trypanothione: a novel bis (glutathionyl) spermidine cofactor for glutathione reductase in trypanosomatids.  Science. 1985;  227 1485-1487
    CrossrefPubMedSearch in Google Scholar
  • 32 Fairlamb A H, Cerami A. Identification of a novel, thiol-containing co-factor essential for glutathione reductase enzyme activity in trypanosomatids.  Mol Biochem Parasitol. 1985;  14 187-198
    CrossrefPubMedSearch in Google Scholar
  • 33 Bond C S, Zhang Y, Berriman M, Cunningham M L, Fairlamb A H, Hunter W H. Crystal structure of Trypanosoma cruzi trypanothione reductase in complex with trypanothione, and the structure-based discovery of new natural product inhibitors.  Structure. 1999;  7 81-89
    CrossrefPubMedSearch in Google Scholar

Prof. Dr. Michael Wink

Institute of Pharmacy and Molecular Biotechnology
Heidelberg University

Im Neuenheimer Feld 364

69120 Heidelberg

Germany

Phone: +49 62 21 54 48 80

Fax: +49 62 21 54 48 84

Email: wink@uni-hd.de