title: Cytotoxic Alkaloids from the Stem of Xylopia laevigata.
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.
authors.affiliation: Department of Chemistry, Federal University of Sergipe, S&#227;o Crist&#243;v&#227;o 49100-000, Sergipe, Brazil. leociley@gmail.com.
authors.forename: Leociley R A
authors.initials: LR
authors.lastname: Menezes
authors.affiliation: Gon&#231;alo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ), Salvador 40000-000, Bahia, Brazil. cnbiologa@gmail.com.
authors.forename: Cinara O D Sousa
authors.initials: CO
authors.lastname: Costa
authors.affiliation: Gon&#231;alo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ), Salvador 40000-000, Bahia, Brazil. anacarolinabcr@gmail.com.
authors.forename: Ana Carolina B da C
authors.initials: AC
authors.lastname: Rodrigues
authors.affiliation: Gon&#231;alo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ), Salvador 40000-000, Bahia, Brazil. felipe.rosario@live.com.
authors.forename: Felipe R do E
authors.initials: FR
authors.lastname: Santo
authors.affiliation: NMR Center, Federal University of Paran&#225;, Curitiba 80000-000, Paran&#225;, Brazil. angelneppel@gmail.com.
authors.forename: Angelita
authors.initials: A
authors.lastname: Nepel
authors.affiliation: NMR Center, Federal University of Paran&#225;, Curitiba 80000-000, Paran&#225;, Brazil. liviamacedodutra@yahoo.com.br.
authors.forename: Lívia M
authors.initials: LM
authors.lastname: Dutra
authors.affiliation: Department of Chemistry, Federal University of Amazonas, Manaus 69000-000, Amazonas, Brazil. felipesaquarema@bol.com.br.
authors.forename: Felipe M A
authors.initials: FM
authors.lastname: Silva
authors.affiliation: Gon&#231;alo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ), Salvador 40000-000, Bahia, Brazil. milenabpsoares@gmail.com.|Center of Biotechnology and Cell therapy, Hospital S&#227;o Rafael, Salvador 40000-000, Bahia, Brazil. milenabpsoares@gmail.com.
authors.forename: Milena B P
authors.initials: MB
authors.lastname: Soares
authors.affiliation: NMR Center, Federal University of Paran&#225;, Curitiba 80000-000, Paran&#225;, Brazil. anderbarison@gmail.com.
authors.forename: Andersson
authors.initials: A
authors.lastname: Barison
authors.affiliation: Department of Chemistry, Federal University of Amazonas, Manaus 69000-000, Amazonas, Brazil. emmanoelvc@gmail.com.
authors.forename: Emmanoel V
authors.initials: EV
authors.lastname: Costa
authors.affiliation: Gon&#231;alo Moniz Institute, Oswaldo Cruz Foundation (IGM-FIOCRUZ), Salvador 40000-000, Bahia, Brazil. danielpbezerra@gmail.com.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Bezerra
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001060:Aporphines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D003603:Cytotoxins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D018922:HL-60 Cells; D056945:Hep G2 Cells; D006801:Humans; D020014:K562 Cells; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D010936:Plant Extracts / Q000737:chemistry; D018547:Plant Stems / Q000737:chemistry*; D061251:Primary Cell Culture; D054336:Xylopia / Q000737:chemistry*
chemical_list: D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D001060:Aporphines; D003603:Cytotoxins; D010936:Plant Extracts; C062700:xylopine
keywords: Annonaceae; Xylopia laevigata; alkaloids; apoptosis; cytotoxicity