Download PDF
Planta Med 2004; 70(1): 45-49
DOI: 10.1055/s-2004-815454
Original Paper
Biochemistry and Molecular Biology
© Georg Thieme Verlag Stuttgart · New York

Rearranged Jatrophane-Type Diterpenes from Euphorbia Species. Evaluation of their Effects on the Reversal of Multidrug Resistance

Ana M. Madureira1 , Maria-José U. Ferreira1 , Nora Gyémánt4 , Katalin Ugocsai4 , José R. Ascenso2 , Pedro M. Abreu3 , Judit Hohmann5 , Joseph Molnár4
  • 1Centro de Estudos de Ciências Farmacêuticas, Faculdade de Farmácia da Universidade de Lisboa, Lisboa, Portugal
  • 2Centro de Química Estrutural, Instituto Superior Técnico, Lisboa, Portugal
  • 3CQFB/REQUIMTE, Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa, Caparica, Portugal
  • 4Department of Medical Microbiology, University of Szeged, Szeged, Hungary
  • 5Department of Pharmacognosy, University of Szeged, Szeged, Hungary
This work was supported by FCT (POCTI, Quadro Comunitário de Apoio III)
Further Information

Publication History

Received: June 6, 2003

Accepted: October 3, 2003

Publication Date:
06 February 2004 (online)

Also available at
    Permissions and Reprints

Abstract

The rearranged jatrophane-type diterpenes (1 - 3), isolated from the Me2CO extracts of Euphorbia portlandica and Euphorbia segetalis, were examined for their effects on multidrug resistance (MDR) in mouse lymphoma cells. Compounds 2 and 3 revealed to be active with the latter being more active than the positive control verapamil, a known resistance modifier. The new compound 1, named portlandicine, was isolated from Euphorbia portlandica and its structure characterised by high-field NMR spectroscopic methods including 2D NMR techniques: COSY, HMQC, HMBC and NOESY. The known diterpene 2, together with aleuritolic acid (4), oleanolic acid (5), and betulin diacetate (6), were also isolated from the same species.

Key words

Euphorbia segetalis - Euphorbia portlandica - Euphorbiaceae - Diterpenes - Jatrophane - Triterpenes - multidrug resistance

References

  • 1 Hohmann J, Vasas A, Günther G, Máthé I, Evanics F, Dombi G, Jerkovitch G. Macrocyclic diterpene polyesters of the jatrophane type from Euphorbia esula .  J Nat Prod. 1997;  60 331-5 and related references cited therein
    CrossrefPubMedSearch in Google Scholar
  • 2 Yamamura S, Kosemura S, Ohba S, Ito M, Saito Y. The isolation and structures of euphoscopins A and B.  Tetrahedron Lett. 1981;  22 5315-8
    CrossrefPubMedSearch in Google Scholar
  • 3 Kupchan S M, Siegel C W, Matz M J, Gilmore C J, Bryan R F. Structure and stereochemistry of jatrophone, a novel macrocyclic diterpenoid tumor inhibitor.  J Am Chem Soc. 1976;  98 2295-300
    CrossrefPubMedSearch in Google Scholar
  • 4 Zheng W F, Cui Z, Zhu Q. Cytotoxic and antiviral activity of the compounds from Euphorbia kansui .  Planta Med. 1998;  64 754-6
    Thieme ConnectPubMedSearch in Google Scholar
  • 5 Hohmann J, Molnár J, Rédei D, Evanics F, Forgo P, Kálmán A, Argay G, Szabó P. Discovery and biological evaluation of a new family of potent modulators of multidrug resistance: reversal of multidrug resistance of mouse lymphoma cells by new natural jatrophane diterpenoids isolated from Euphorbia species.  J Med Chem. 2002;  45 2425-31
    CrossrefPubMedSearch in Google Scholar
  • 6 Kim S E, Hong Y S, Kim Y C, Lee J J. Mode of action of torilim in multidrug-resistance cancer cell lines.  Planta Med. 1998;  64 335-8
    PubMedSearch in Google Scholar
  • 7 Wiese M, Pajeva I K. Structure-activity relationships of multidrug resistance reversers.  Curr Med Chem. 2001;  8 685-713
    CrossrefPubMedSearch in Google Scholar
  • 8 Ferreira M JU, Madureira A M, Ascenso J R. A tetracyclic diterpene and triterpenes from Euphorbia segetalis .  Phytochemistry. 1998;  49 79-83
    CrossrefPubMedSearch in Google Scholar
  • 9 Jakupovic J, Jeske F, Morgenstern T, Tsichritzis F, Marco J A, Berendsohn W. Diterpenes from Euphorbia segetalis .  Phytochemistry. 1998;  47 583-1600
    CrossrefPubMedSearch in Google Scholar
  • 10 Coenwell M M, Pastan I, Gottesmann M M. Certain calcium channel blockers bind specifically to multidrug-resistance human KB carcinoma membrane vesicles and inhibit drug binding to P-glycoprotein.  J Biol Chem. 1987;  262 2166-70
    PubMedSearch in Google Scholar
  • 11 Weaver J L, Szabo G, Pine P S, Gottesman M M, Goldenberg S, Aszalos A. The effect of ion channel blockers, immunosuppressive agents, and other drugs on the activity of the multidrug transporter.  Int J Cancer. 1993;  54 456-61
    PubMedSearch in Google Scholar
  • 12 Kessel D. Exploring multidrug resistance using Rhodamine 123.  Cancer Commun. 1989;  1 145-9
    PubMedSearch in Google Scholar
  • 13 Jakupovic J, Morgenstern T, Marco J A, Berendsohn W. Diterpenes from Euphorbia paralias .  Phytochemistry. 1998;  47 1611-9
    CrossrefPubMedSearch in Google Scholar
  • 14 Liu L G, Tan R X. New jatrophane diterpenoid esters from Euphorbia turczaninowii .  J Nat Prod. 2001;  64 1064-8 and related references cited therein
    CrossrefPubMedSearch in Google Scholar
  • 15 Chaudhuri S K, Fullas D, Brown D M, Wani M C, Wall M E. Isolation and structural elucidation of pentacyclic triterpenoids from Maprounea africana .  J Nat Prod. 1995;  58 1-9
    CrossrefPubMedSearch in Google Scholar
  • 16 Ikuta A, Itokawa H. Triterpenoids of Paeonia japonica callus tissue.  Phytochemistry. 1988;  27 2813-5
    CrossrefPubMedSearch in Google Scholar
  • 17 Teresa J P, Urones J G, Marcos I S, Basabe P, Cuadrado M JS, Moro R F. Triterpenes from Euphorbia broteri .  Phytochemistry. 1987;  26 1767-76
    CrossrefPubMedSearch in Google Scholar
  • 18 Budzikiewicz H, Wilson J M, Djerassi C. Mass spectrometry in structural and stereochemical problems. XXXII. Pentacyclic triterpenes.  J Am Chem Soc. 1963;  85 3688-99
    PubMedSearch in Google Scholar

Prof. Maria José Umbelino Ferreira

Centro de Estudos de Ciências Farmacêuticas

Faculdade de Farmácia da Universidade de Lisboa

Av. das Forças Armadas

1600-083 Lisboa

Portugal

Fax: +351-21-7946470

Email: mjuferreira@ff.ul.pt