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Further drimane sesquiterpenes from Drimys brasiliensis stem barks with cytotoxic potential

  • Eduarda Fratoni
  • Vanessa Duarte Claudino
  • Rosendo Augusto Yunes
  • Gilberto C. FranchiJr.
  • Alexandre E. Nowill
  • Valdir Cechinel Filho
  • Franco Delle Monache
  • Angela MalheirosEmail author
Original Article

Abstract

Drimys brasiliensis Miers (Winteraceae) is used in folk medicine for the treatment of cancer. Its anti-tumor activity has been demonstrated in vitro models using extracts and isolated compounds. This study investigates the cytotoxic effects of stem bark extracts of D. brasiliensis as well as isolated compounds that may be responsible for the activitys and evaluates them in leukemia cells. The stem bark extract were subjected to column chromatography, and the structures of compounds were elucidated based on spectroscopic methods by using NMR and infrared spectroscopy and GC/MS. The cytotoxicity of the isolated compounds was evaluated in chronic myeloid (K562) and acute B lymphoblastic (Nalm6) leukemia cells using tetrazolium assay (MTT). Two new compounds were isolated 1β-O-p-methoxy-E-cinnamoyl-5α-keto-11α-enol-albicanol (1a) and the isomer 1β-O-p-methoxy-E-cinnamoyl-5α-keto-11β-enol-albicanol (1b) and 1β-O-p-methoxy-E-cinnamoyl-isodrimeninol (2). The known compounds polygonal acid (3a) and the isomer isopolygonal acid (3b), fuegin (4a) and the isomer epifuegin (4b), the mixture drimanial (5) and 1β-O-(p-methoxy-E-cinnamoyl)-6α-hydroxypolygodial (6) were also isolated. The drimanes (1-4) and drimanial (5), 1β-(p-coumaroyloxy)-polygodial (7), 1β-(p-methoxycinnamoyl)-polygodial (8), and polygodial (9) isolated previously were assessed in tumor cells. The IC50 values were between 3.56 and 128.91 μM. 1-β-(p-cumaroiloxi)-polygodial showed the best result with IC50 8.18 and 3.56 μM by K562 and Nalm6, respectively. The chloroform extract of the stem bark of D. brasiliensis is a great source of drimane sesquiterpenes. Our experimental data suggest that drimanes are responsible for cytotoxicity activity demonstrated by this species, especially those with the aldehyde group linked to carbons C-11 and C-12.

Keywords

Chromatography Cytotoxic potential Drimys brasiliensis Phytochemistry Sesquiterpenoids 

Abstract

Drimys brasiliensis Miers (Winteraceae) is used in folk medicine for the treatment of cancer. Its anti-tumor activity has been demonstrated in vitro models using extracts and isolated compounds. This study investigates the cytotoxic effects of stem bark extracts of D. brasiliensis as well as isolated compounds that may be responsible for the activity and evaluates them in leukemia cells. The stem bark extracts were subjected to column chromatography, and the structures of compounds were elucidated based on spectroscopic methods by using NMR and infrared spectroscopy and GC/MS. The cytotoxicity of the isolated compounds was evaluated in chronic myeloid (K562) and acute B lymphoblastic (Nalm6) leukemia cells using tetrazolium assay (MTT). Two new compounds were isolated 1β-O-p-methoxy-E-cinnamoyl-5α-keto-11α-enol-albicanol (1a) and the isomer 1β-O-p-methoxy-E-cinnamoyl-5α-keto-11β-enol-albicanol (1b) and 1β-O-p-methoxy-E-cinnamoyl-isodrimeninol (2). The known compounds polygonal acid (3a) and the isomer isopolygonal acid (3b), fuegin (4a) and the isomer epifuegin (4b), and the mixture drimanial (5) and 1β-O-(p-methoxy-E-cinnamoyl)-6α-hydroxypolygodial (6) were also isolated. The drimanes (1–4) and drimanial (5), 1β-(p-coumaroyloxy)-polygodial (7), 1β-(p-methoxycinnamoyl)-polygodial (8), and polygodial (9) isolated previously were assessed in tumor cells. The IC50 values were between 3.56 and 128.91 μM. 1-β-(p-Cumaroiloxi)-polygodia showed the best result with IC50 8.18 and 3.56 μM by K562 and Nalm6, respectively. The chloroform extract of the stem bark of D. brasiliensis is a great source of drimane sesquiterpenes. Our experimental data suggest that drimanes are responsible for cytotoxicity activity demonstrated by this species, especially those with the aldehyde group linked to carbons C-11 and C-12.

Notes

Acknowledgments

The authors thank the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Apoio à Pesquisa Científica e Tecnológica do Estado de Santa Catarina (FAPESC), Programa Iberoamericano de Ciência y Tecnologia para el Desarrollo (CYTED) – Red 0464 RIBECANCER, and the University of Vale do Itajaí (UNIVALI) for their financial support.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Eduarda Fratoni
    • 1
  • Vanessa Duarte Claudino
    • 1
  • Rosendo Augusto Yunes
    • 2
  • Gilberto C. FranchiJr.
    • 3
  • Alexandre E. Nowill
    • 3
  • Valdir Cechinel Filho
    • 1
  • Franco Delle Monache
    • 1
  • Angela Malheiros
    • 1
    Email author
  1. 1.Programa de Pós-Graduação em Ciências Farmacêuticas e Núcleo de Investigações Químico-FarmacêuticasUniversidade do Vale do Itajaí – UNIVALIItajaíBrazil
  2. 2.Programa de Pós-Graduação em QuímicaUniversidade Federal de Santa Catarina – UFSCFlorianópolisBrazil
  3. 3.Centro Integrado de Pesquisas Oncohematológicas na Infância (CIPOI)UNICAMPCampinasBrazil

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