2. Academic Validation
  3. Cytotoxic Alkaloids from the Stem of Xylopia laevigata

Cytotoxic Alkaloids from the Stem of Xylopia laevigata

  • Molecules. 2016 Jul 8;21(7):890. doi: 10.3390/molecules21070890.
Leociley R A Menezes 1,  Cinara O D Sousa Costa 2,  Ana Carolina B da C Rodrigues 3,  Felipe R do E Santo 4,  Angelita Nepel 5,  Lívia M Dutra 6,  Felipe M A Silva 7,  Milena B P Soares 8 9,  Andersson Barison 10,  Emmanoel V Costa 11,  Daniel P Bezerra 12
Affiliations

Affiliations

  • 1 Department of Chemistry, Federal University of Sergipe, São Cristóvão 49100-000, Sergipe, Brazil. leociley@gmail.com.
  • 2 Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ), Salvador 40000-000, Bahia, Brazil. cnbiologa@gmail.com.
  • 3 Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ), Salvador 40000-000, Bahia, Brazil. anacarolinabcr@gmail.com.
  • 4 Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ), Salvador 40000-000, Bahia, Brazil. felipe.rosario@live.com.
  • 5 NMR Center, Federal University of Paraná, Curitiba 80000-000, Paraná, Brazil. angelneppel@gmail.com.
  • 6 NMR Center, Federal University of Paraná, Curitiba 80000-000, Paraná, Brazil. liviamacedodutra@yahoo.com.br.
  • 7 Department of Chemistry, Federal University of Amazonas, Manaus 69000-000, Amazonas, Brazil. felipesaquarema@bol.com.br.
  • 8 Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ), Salvador 40000-000, Bahia, Brazil. milenabpsoares@gmail.com.
  • 9 Center of Biotechnology and Cell therapy, Hospital São Rafael, Salvador 40000-000, Bahia, Brazil. milenabpsoares@gmail.com.
  • 10 NMR Center, Federal University of Paraná, Curitiba 80000-000, Paraná, Brazil. anderbarison@gmail.com.
  • 11 Department of Chemistry, Federal University of Amazonas, Manaus 69000-000, Amazonas, Brazil. emmanoelvc@gmail.com.
  • 12 Gonçalo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ), Salvador 40000-000, Bahia, Brazil. danielpbezerra@gmail.com.
PMID: 27399666 DOI: 10.3390/molecules21070890
Abstract

Xylopia laevigata (Annonaceae), known locally as "meiú" or "pindaíba", is widely used in folk medicine in Northeastern Brazil. In the present work, we performed phytochemical analyses of the stem of X. laevigata, which led to the isolation of 19 alkaloids: (-)-roemerine, (+)-anonaine, lanuginosine, (+)-glaucine, (+)-xylopine, oxoglaucine, (+)-norglaucine, asimilobine, (-)-xylopinine, (+)-norpurpureine, (+)-N-methyllaurotetanine, (+)-norpredicentrine, (+)-discretine, (+)-calycinine, (+)-laurotetanine, (+)-reticuline, (-)-corytenchine, (+)-discretamine and (+)-flavinantine. The in vitro cytotoxic activity toward the tumor cell lines B16-F10 (mouse melanoma), HepG2 (human hepatocellular carcinoma), K562 (human chronic myelocytic leukemia) and HL-60 (human promyelocytic leukemia) and non-tumor peripheral blood mononuclear cells (PBMCs) was tested using the Alamar Blue assay. Lanuginosine, (+)-xylopine and (+)-norglaucine had the highest cytotoxic activity. Additionally, the pro-apoptotic effects of lanuginosine and (+)-xylopine were investigated in HepG2 cells using LIGHT and fluorescence microscopies and flow cytometry-based assays. Cell morphology consistent with Apoptosis and a marked phosphatidylserine externalization were observed in lanuginosine- and (+)-xylopine-treated cells, suggesting induction of apoptotic cell death. In addition, (+)-xylopine treatment caused G₂/M cell cycle arrest in HepG2 cells. These data suggest that X. laevigata is a potential source for cytotoxic Alkaloids.

Keywords

Annonaceae; Xylopia laevigata; alkaloids; apoptosis; cytotoxicity.

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