Download PDF
Planta Med 2005; 71(1): 54-58
DOI: 10.1055/s-2005-837751
Original Paper
Natural Product Chemistry
© Georg Thieme Verlag KG Stuttgart · New York

A Cytotoxic Meroterpenoid Benzoquinone from Roots of Cordia globosa

Jane Eire S. Alencar de Menezes1 , Telma Leda G. Lemos1 , Otília Deusdênia L. Pessoa1 , Raimundo Braz-Filho2 , Raquel C. Montenegro3 , Diego Veras Wilke3 , Letícia V. Costa-Lotufo3 , Cláudia Pessoa3 , Manoel Odorico de Moraes3 , Edilberto R. Silveira1
  • 1Curso de Pós-Graduação em Química Orgânica, Departamento de Química Orgânica e Inorgânica, Centro de Ciências, Universidade Federal do Ceará, Fortaleza, Ceará, Brasil
  • 2Setor de Química de Produtos Naturais - LCQUI - CCT, Universidade Estadual do Norte Fluminense, Rio de Janeiro, Brasil
  • 3Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, Ceará, Brasil
Further Information

Publication History

Received: April 19, 2004

Accepted: August 31, 2004

Publication Date:
27 January 2005 (online)

Also available at
    Permissions and Reprints

Abstract

(1aS*,1bS*,7aS*,8aS*)-4,5-Dimethoxy-1a,7a-dimethyl-1,1a,1b,2,7, 7a,8,8a-octahydrocyclopropa[3] [4]cyclopenta[1,2-b]naphthalene-3,6-dione (1), a new meroterpenoid benzoquinone, and microphyllaquinone (2), a known naphthoquinone, have been isolated from roots of Cordia globosa. Both structure determinations were performed by conventional spectroscopic methods, including inverse detection NMR techniques, and by comparison with data from the literature for related compounds. Compound 1 displayed considerable cytotoxic activity against several cancer cell lines with IC50 values in the range of 1.2 to 5.0 μg/mL. The cytotoxic activity seemed to be related to DNA synthesis inhibition, as revealed by the reduction of 5-bromo-2′-deoxyuridine incorporation, and apoptosis induction, as indicated by the acridine orange/ethidium bromide assay and morphological changes after 24 h of incubation on leukemic cells.

Key words

Cordia globosa - Boraginaceae - benzoquinone - naphthoquinone - cytotoxic activity

References

  • 1 Kuroyanagi M, Seki T, Hayashi T, Nagashima Y, Kawahara N, Sekita S, Satake M. Anti-androgenic triterpenoids from Brazilian medicinal plant.  Chem Pharm Bull. 2001;  49 954-7
    CrossrefPubMedSearch in Google Scholar
  • 2 Menezes J ESA, Lemos T LG, Silveira E R, Braz-Filho R, Pessoa O DL. Trichotomol, a new cadinenediol from Cordia trichotoma .  J Braz Chem Soc. 2001;  12 787-90
    PubMedSearch in Google Scholar
  • 3 Sertié J AA, Basile A C, Panizza S, Matida A K, Zelnik R. Anti-inflammatory activity and sub-acute toxicity of artemetin.  Planta Medica. 1990;  56 36-40
    PubMedSearch in Google Scholar
  • 4 Manners G D. The hydroquinone terpenoids of Cordia elaeagnoides . J Chem Soc Perkin Trans I 1983: 39-43
    Search in Google Scholar
  • 5 Santos R P, Viana F A, Lemos T LG, Silveira E R, Braz-Filho R, Pessoa O DL. Structure elucidation and total assignment of 1H and 13C NMR data for a new bisdesmoside saponin from Cordia piauhiensis .  Magn Reson Chem. 2003;  41 735-8
    CrossrefPubMedSearch in Google Scholar
  • 6 Moir M, Thomson R H. Naturally occurring quinones. Part XXII. Terpenoid Quinones in Cordia spp. J Chem Soc Perkin Trans I 1973: 1352-7
    Search in Google Scholar
  • 7 Ioset J R, Marston A, Gupta M P, Hostettmann K. Antifungal and larvicidal cordiaquinones from the roots of Cordia curassavica .  Phytochemistry. 2000;  53 613-7
    CrossrefPubMedSearch in Google Scholar
  • 8 Silva S AS, Rodrigues M SL, Agra M F, da-Cunha E VL, Barbosa-Filho J, Silva M S. Flavonoids from Cordia globosa .  Biochem Syst Ecol. 2004;  32 359-61
    PubMedSearch in Google Scholar
  • 9 Costa-Lotufo L V, Ferreira M AD, Lemos T LG, Pessoa O DL, Viana G SB, Cunha G MA. Toxicity to sea urchin egg development of the quinone fraction obtained from Auxemma oncocalyx .  Braz J Med Biol Res. 2002;  35 927-30
    PubMedSearch in Google Scholar
  • 10 Santos H S, Costa S MO, Pessoa O DL, Moraes M O, Pessoa C, Fortier S, Silveira E R, Lemos T LG. Cytotoxic naphthoquinones from roots of Lippia microphylla .  Z Naturforsch. 2003;  58c 517-20
    PubMedSearch in Google Scholar
  • 11 Veras M L, Bezerra M ZB, Braz-Filho R, Pessoa O DL, Montenegro R C, Pessoa C, Moraes M O, Costa-Lotufo L V. Cytotoxic epimeric withaphysalins from leaves of Acnistus arborescens (Solanaceae).  Planta Med. 2004;  70 551-5
    Thieme ConnectPubMedSearch in Google Scholar
  • 12 Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.  J Immunol Meth. 1983;  16 55-63
    PubMedSearch in Google Scholar
  • 13 Renzi D, Valtolina M, Foster R. The evaluation of a multi-endpoint cytotoxicity assay system.  ATLA. 1993;  21 89-96
    PubMedSearch in Google Scholar
  • 14 Cury-Boaventura M F, Pompéia C, Curi R. Comparative toxicity of oleic acid and linoleic acid on Jurkat cells.  Clin Nut. 2004;  23 721-32
    PubMedSearch in Google Scholar
  • 15 Pera F, Mattias P, Detzer K. Methods for determining the proliferation kinetics of cells by means of 5-bromodeoxyuridine.  Cell Tissue Kinet. 1977;  10 255-64
    PubMedSearch in Google Scholar
  • 16 Guntern A, Ioset J R, Queiroz E F, Foggin C M, Hostettmann K. Quinones from Heliotropium ovalifolium .  Phytochemistry. 2001;  58 631-5
    CrossrefPubMedSearch in Google Scholar
  • 17 Moir M, Thomson R H, Hausen B M, Simatupang M H. Cordiachromes: a new group of terpenoid quinones from Cordia spp. J Chem Soc Chem Commun 1972: 363-364
    Search in Google Scholar
  • 18 Fourie J, Guziec Jr F, Guziec L, Monterrosa C, Fiterman D J, Begleiter A. Structure-activity study with bioreductive benzoquinone alkylating agents: effects on DT-diaphorase-mediated DNA crosslink and strand break formation in relation to mechanisms of cytotoxicity.  Cancer Chemother Pharmacol. 2004;  53 191-203
    CrossrefPubMedSearch in Google Scholar
  • 19 Benchekroun M N, Myers C E, Sinha B K. Free radical formation by ansamycin benzoquinone in human breast tumor cells: implications for cytotoxicity and resistance.  Free Radic Biol Med. 1994;  17 191-200
    CrossrefPubMedSearch in Google Scholar
  • 20 Sinha B K. Free radicals in anticancer drug pharmacology.  Chem Biol Interact. 1989;  69 293-17
    PubMedSearch in Google Scholar

Dr. Otília Deusdênia L. Pessoa

Departamento de Química Orgânica e Inorgânica

Centro de Ciências

Universidade Federal do Ceará

Caixa Postal 12200

CEP 60021-970 Fortaleza-CE

Brasil

Phone: +55-85-288-9441

Fax: +55-85-288-9782

Email: opessoa@ufc.br