Introduction Aiouea trinervis Meisn. (Lauraceae), a shrub found in the ªcerra- doº of Mato Grosso do Sul, Brazil, is considered an endangered species. Even though it belongs to a widely studied plant family known for providing a number of bioactive secondary metabo- lites, the genus Aiouea had not been chemically investigated pre- viously. In the search for potential natural product-derived anti- tumor agents from plants endemic to the west-central region of Brazil, we found that the ethanolic extracts of the roots and un- derground trunk of this plant showed significant activity in the brine shrimp (Artemia salina) lethality assay (LD 50 = 1.93 and 0.92 mg/mL, respectively). The ethanolic extract of its leaves was only weakly active (LD 50 = 262.1 mg/mL). Fractionation of the ex- tracts led to the isolation of four butanolides, namely (±)-epilitse- nolides C 2 and C 1 (1 and 2), isoobtusilactone A (3) and obtusilac- toneA(4);twoknownlignans,(+)-sesamin(5) and (+)-methylpi- peritol (6); and polyprenol-12 (7). Compounds 1 and 2 are re- ported here for the first time as genuine natural products. Here- in, we report the isolation of these compounds and the evalua- tion of the cytotoxic activities of 1 , 2, 3,5 and 6 against Hep 2 hu- man cancer cell lines as well as the genotoxic effects of the crude Cytotoxic and Genotoxic Butanolides and Lignans from Aiouea trinervis F. R. Garcez 1 W. S. Garcez 1 M. Martins 1 M. F. C. Matos 2 Z. R. Guterres 3 M. S. Mantovani 4 C. K. Misu 2 S. T. Nakashita 2 Affiliation 1 Department of Chemistry, Federal University of Mato Grosso do Sul (UFMS), Campo Grande, MS, Brazil 2 DepartmentofPharmacyandBiochemistry,FederalUniversityofMatoGrossodoSul(UFMS),CampoGrande, MS, Brazil 3 State University of Mato Grosso do Sul, Coxim, MS, Brazil 4 Department of Biological Sciences, State University of Londrina, Londrina, PR, Brazil Correspondence Dr. Fernanda Rodrigues Garcez ´ Universidade Federal de Mato Grosso do Sul ´ CCET ´ Departamento de Química ´ Cidade Universitµria ´ Campo Grande ´ MS79070±900 ´ Brazil ´ Phone: +55-67-345-3559 ´ Fax: +55-67-345-3552 ´ E-mail: frgarcez@nin.ufms.br Received December 17, 2004 ´ Accepted April 13, 2005 Bibliography Planta Med 2005; 71: 923±927 ´  Georg Thieme Verlag KG Stuttgart ´ New York DOI 10.1055/s-2005-871251 ´ Published online September 19, 2005 ISSN 0032-0943 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 :1.93,0.92and262.1 mg/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)andpoly- prenol-12 (7) were isolated as well. Their structures were deter- mined with spectral methods (1D-, 2D-NMR and MS). Com- pounds 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 mg/mL and 4.95 mg/mL, respectively) whereas the other compounds showed moderate IC 50 values ranging from 12.20 mg/mL to 25.64 mg/mL. The genotoxic proper- ties of the crude ethanolic extracts and of compounds 3 and 5 were also evaluated in this study on CHO K1 and HTC mamma- lian 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). Key words Aiouea trinervis ´ Lauraceae ´ (±)-epilitsenolides C 1 and C 2 ´ cyto- toxic activity ´ genotoxic activity ´ comet assay Original Paper 923 Downloaded by: IP-Proxy CONSORTIUM:CAPES (UEL Universidade Estadual De Londrina), null. Copyrighted material.