Download PDF
Planta Med 2020; 86(01): 55-60
DOI: 10.1055/a-1021-0611
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Eglerisine, a Novel Sesquiterpenoid Tropolone from Dulacia egleri with Antiproliferative Effect against an Acute Myeloid Leukemia Lineage

Leice M. R. de Novais
1   Departamento de Química, Universidade Federal de Mato Grosso, Cuiabá, MT, Brazil
,
Luiz F. Ferreira
1   Departamento de Química, Universidade Federal de Mato Grosso, Cuiabá, MT, Brazil
,
Paulo T. de Sousa Jr.
1   Departamento de Química, Universidade Federal de Mato Grosso, Cuiabá, MT, Brazil
,
Tereza A. N. Ribeiro
1   Departamento de Química, Universidade Federal de Mato Grosso, Cuiabá, MT, Brazil
,
Marcos J. Jacinto
1   Departamento de Química, Universidade Federal de Mato Grosso, Cuiabá, MT, Brazil
,
Carlos H. C. dos Santos
2   Departamento de Química, Universidade Federal Rural do Rio de Janeiro, Seropédica, RJ, Brazil
,
Mário G. de Carvalho
2   Departamento de Química, Universidade Federal Rural do Rio de Janeiro, Seropédica, RJ, Brazil
,
Heron F. V. Torquato
3   Departamento de Bioquímica, Universidade Federal de São Paulo, São Paulo, SP, Brazil
4   Faculdade de Farmácia, Braz Cubas Educação, Mogi das Cruzes, SP, Brazil
,
Edgar J. Paredes-Gamero
3   Departamento de Bioquímica, Universidade Federal de São Paulo, São Paulo, SP, Brazil
5   Faculdade de Ciências Farmacêuticas, Alimentos e Nutrição (FACFAN), Universidade Federal de Mato Grosso do Sul, Campo Grande, MS, Brazil
,
Virgínia C. P. Silva
1   Departamento de Química, Universidade Federal de Mato Grosso, Cuiabá, MT, Brazil
› Author Affiliations
Further Information

Publication History

received 19 April 2019
revised 23 September 2019

accepted 30 September 2019

Publication Date:
17 October 2019 (online)

Also available at
    Permissions and Reprints

Abstract

Chemical investigation of the stems of Dulacia egleri resulted in the isolation of eglerisine (1), a compound with a rare sesquiterpenoid tropolone skeleton. Its structure was determined by analysis of spectrometric and spectroscopic data, including HRESIMS, 1D, and 2D NMR. The antiproliferative effects of eglerisine were tested in human leukemia lineages. In the Kasumi-1 lineage, an acute myeloid leukemia cell line, eglerisine reduced cell metabolism, as determined by the resazurin assay. Eglerisine did not induce cell death by either apoptotic or necrotic mechanisms. However, a reduction of the absolute number of cells was observed. Eglerisine induced cell cycle arrest after 72 h of treatment by phosphorylation of H2AX histone, reducing the S phase and increasing the G2 phase of the cell cycle.

Key words

Dulacia egleri - Olacaceae - tropolone sesquiterpene - cell cycle arrest

Supporting Information

    1D and 2D NMR spectra and HRESIMS spectrum, as well as proliferation inhibition curves of eglerisine (1) against human leukemia cell lines, are available as Supporting Information.

  • Supporting Information
 

  • References

  • 1 Rossi L. Olacaceae in Lista de Espécies da Flora do Brasil. Jardim Botânico do Rio de Janeiro. Available at: http://floradobrasil.jbrj.gov.br/jabot/floradobrasil/FB175 Accessed February 1, 2019
    PubMed
  • 2 Sleumer HO. Olacaceae. Fl Neotrop Monogr, v. 38: 121.
    PubMed
  • 3 Picerno P, Mencherini T, Rastrelli L, Piccinelli A, Aquino R. Isoprenoid glycosides from Liriosma ovata . J Nat Prod 2008; 71: 265-268
    CrossrefPubMedSearch in Google Scholar
  • 4 Ma J, Pawar RS, Grundel E, Mazzola EP, Ridge CD, Masaoka T, Le Grice SF, Wilson J, Beutler JA, Krynitsky AJ. Sesquiterpenoid tropolone glycosides from Liriosma ovata . J Nat Prod 2014; 78: 315-319
    PubMedSearch in Google Scholar
  • 5 Polonsky J, Varenne J, Prangé T, Pascard C, Jacquemin H, Fournet AJ. Isolation and structure (X-ray analysis) of manicoline A, a new α-aminotropone from Dulacia guianensis (Olacaceae). J Chem Soc Chem Commun 1981; 15: 731-732
    PubMedSearch in Google Scholar
  • 6 Polonsky J, Beloeil JC, Prangé T, Pascard C, Jacquemin H, Donnelly DMX, Kenny PTM. Manicol: a sesquiterpenoid hydroxytropolone from Dulacia guianensis; a revised structure (x-ray analysis). Tetrahedron 1983; 39: 2647-2655
    CrossrefPubMedSearch in Google Scholar
  • 7 Polonsky J, Varenne J, Prangé T, Pascard C, Jacquemin H, Fournet A. Structure (X-ray analysis) of manicoline B, a mixture of two diastereoisomers of a new alkaloid from Dulacia guianensis (Olacaceae). Tetrahedron Lett 1984; 25: 2359-2362
    CrossrefPubMedSearch in Google Scholar
  • 8 Ichado CLF, Costa CG, Abreu CLB. Arquivos do Jardim Botânico do Rio de Janeiro, Vol. XX. Brasil: Ministério da Agricultura; 1977: 199
    Search in Google Scholar
  • 9 Pott A, Pott V. Plantas do Pantanal. Brasil: EMBRAPA – Centro de Pesquisa Agropecuária do Pantanal, Brasília; 1994: 222
    Search in Google Scholar
  • 10 de Novais LMR, de Arueira CCO, Ferreira LF, Ribeiro TAN, Sousa jr. PT, Jacinto MJ, de Carvalho MG, Judice WAS, Jesus LOP, de Souza AA, Torquato HFV, Paredes-Gamero EJ, Silva VC. 4′-Hydroxy-6,7-methylenedioxy-3-methoxyflavone: A novel flavonoid from Dulacia egleri with potential inhibitory activity against cathepsins B and L. Fitoterapia 2019; 132: 26-29
    CrossrefPubMedSearch in Google Scholar
  • 11 Liu N, Song W, Schienebeck CM, Zhang M, Tang W. Synthesis of naturally occurring tropones and tropolones. Tetrahedron 2014; 70: 9281-9305
    CrossrefPubMedSearch in Google Scholar
  • 12 Bentley R. A fresh look at natural tropolonoids. Nat Prod Rep 2008; 25: 118-138
    CrossrefPubMedSearch in Google Scholar
  • 13 Grant S. Ara-C: cellular and molecular pharmacology. Adv Cancer Res 1998; 72: 197-233
    PubMedSearch in Google Scholar
  • 14 Torquato HFV, Ribeiro-Filho AC, Buri MV, Araújo jr. RT, Pimenta R, de Oliveira JS, Filho VC, Macho A, Paredes-Gamero EJ, Martins DTO. Canthin-6-one induces cell death, cell cycle arrest and differentiation in human myeloid leukemia cells. Biochim Biophys Acta Gen Subj 1861; 4: 958-967
    PubMedSearch in Google Scholar
  • 15 Vital WD, Torquato HFV, Jesus LOP, Judice WAS, Silva MFDGFD, Rodrigues T, Justo GZ, Veiga TAM, Paredes-Gamero EJ. 4-Deoxyraputindole C induces cell death and cell cycle arrest in tumor cell lines. J Cell Biochem 2018; 120: 9608-9623
    PubMedSearch in Google Scholar
  • 16 Burma S, Chen BP, Murphy M, Kurimasa A, Chen DJ. ATM phosphorylates histone H2AX in response to DNA double-strand breaks. J Biol Chem 2001; 276: 42462-42467
    Search in Google Scholar
  • 17 Zhao J. Plant troponoids: chemistry, biological activity, and biosynthesis. Curr Med Chem 2007; 14: 2597-2621
    CrossrefPubMedSearch in Google Scholar
  • 18 Ononye SN, VanHeyst MD, Oblak EZ, Zhou W, Ammar M, Anderson AC, Wright DL. Tropolones as lead-like natural products: the development of potent and selective histone deacetylase inhibitors. ACS Med Chem Lett 2013; 4: 757-761
    CrossrefPubMedSearch in Google Scholar
  • 19 Hsiao CJ, Hsiao SH, Chen WL, Guh JH, Hsiao G, Chan YJ, Lee TH, Chung CL. Pycnidione, a fungus-derived agent, induces cell cycle arrest and apoptosis in A549 human lung cancer cells. Chem Biol Interact 2012; 15: 23-30
    PubMedSearch in Google Scholar
  • 20 Morita Y, Matsumura E, Okabe T, Fukui T, Ohe T, Ishida N, Inamori Y. Biological activity of β-dolabrin, γ-thujaplicin, and 4-cetyltropolone, hinokitiol-related compounds. Biol Pharm Bull 2004; 27: 1666-1669
    CrossrefPubMedSearch in Google Scholar
  • 21 Doulias PT, Nousis L, Zhu BZ, Frei B, Galaris D. Protection by tropolones against H2O2-induced DNA damage and apoptosis in cultured Jurkat cells. Free Radical Res 2005; 39: 125-135
    CrossrefPubMedSearch in Google Scholar
  • 22 Li J, Falcone ER, Holstein SA, Anderson AC, Wright DL, Wiemer AJ. Novel α-substituted tropolones promote potent and selective caspase-dependent leukemia cell apoptosis. Pharmacol Res 2016; 113: 438-448
    CrossrefPubMedSearch in Google Scholar
  • 23 Cao L, Kuratnik A, Xu W, Gibson JD, Kolling FT, Falcone ER, Ammar M, Van Heyst MD, Wright DL, Nelson CE, Giardina C. Development ofintestinal organoids as tissue surrogates: cell composition and the epigenetic control of differentiation. Mol Carcinog 2015; 54: 189-202
    CrossrefPubMedSearch in Google Scholar
  • 24 Guo H, Roman D, Beemelmanns C. Tropolone natural products. Nat Prod Rep 2019; 36: 1137-1155
    CrossrefPubMedSearch in Google Scholar
  • 25 Liu S, Yamauchi H. Hinokitiol, a metal chelator derived from natural plants, suppresses cell growth and disrupts androgen receptor signaling in prostate carcinoma cell lines. Biochem Biophys Res Commun 2006; 351: 26-32
    CrossrefPubMedSearch in Google Scholar