title: Cytotoxic and genotoxic butanolides and lignans from Aiouea trinervis.
abstract: The ethanolic extracts from the roots, the underground trunk and the leaves of Aiouea trinervis were active in the brine shrimp (Artemia salina) lethality assay (LD (50): 1.93, 0.92 and 262.1 microg/mL, respectively). Fractionation of the extracts led to the isolation of four butanolides, namely (-)-epilitsenolides C (2) and C (1) ( 1 and 2), isoobtusilactone A ( 3) and obtusilactone A ( 4), two of which ( 1 and 2) are reported for the first time as genuine natural products. The lignans (+)-sesamin ( 5) and (+)-methylpiperitol ( 6) and polyprenol-12 ( 7) were isolated as well. Their structures were determined with spectral methods (1D-, 2D-NMR and MS). Compounds 1, 2, 3, 5 and 6 were tested for their cytotoxic activities in Hep (2) human cancer cells. The butanolides 2 and 3 were the most active (IC (50): 5.96 microg/mL and 4.95 microg/mL, respectively) whereas the other compounds showed moderate IC (50) values ranging from 12.20 microg/mL to 25.64 microg/mL. The genotoxic properties of the crude ethanolic extracts and of compounds 3 and 5 were also evaluated in this study on CHO K1 and HTC mammalian cells with single-cell gel electrophoresis (comet assay). The crude extracts as well as the compounds tested induced DNA migration in this assay, which was indicative of DNA damage (genotoxic effect).
authors.affiliation: Department of Chemistry, Federal University of Mato Grosso do Sul (UFMS), Campo Grande, MS 79070-900, Brazil. frgarcez@nin.ufms.br
authors.forename: F R
authors.initials: FR
authors.lastname: Garcez
authors.forename: W S
authors.initials: WS
authors.lastname: Garcez
authors.forename: M
authors.initials: M
authors.lastname: Martins
authors.forename: M F C
authors.initials: MF
authors.lastname: Matos
authors.forename: Z R
authors.initials: ZR
authors.lastname: Guterres
authors.forename: M S
authors.initials: MS
authors.lastname: Mantovani
authors.forename: C K
authors.initials: CK
authors.lastname: Misu
authors.forename: S T
authors.initials: ST
authors.lastname: Nakashita
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001156:Artemia / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D019770:Lauraceae; D017705:Lignans / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D009153:Mutagens / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018515:Plant Leaves; D018517:Plant Roots
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017705:Lignans; D009153:Mutagens; D010936:Plant Extracts