Cytotoxic and genotoxic butanolides and lignans from Aiouea trinervis.
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).
Garcez
F R
FR
Department of Chemistry, Federal University of Mato Grosso do Sul (UFMS), Campo Grande, MS 79070-900, Brazil. frgarcez@nin.ufms.br
Garcez
W S
WS
Martins
M
M
Matos
M F C
MF
Guterres
Z R
ZR
Mantovani
M S
MS
Misu
C K
CK
Nakashita
S T
ST
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
D000972:Antineoplastic Agents, Phytogenic; D017705:Lignans; D009153:Mutagens; D010936:Plant Extracts