title: Mutagenicity and recombinagenicity of Ocotea acutifolia (Lauraceae) aporphinoid alkaloids.
abstract: The somatic mutation and recombination test (SMART) in wing cells of Drosophila melanogaster was used to test the mutagenic and recombinogenic activities of five aporphinoid alkaloids isolated from Ocotea acutifolia: thalicminine (1), (+)-dicentrine (2), (+)-ocoteine (3), (+)-6S-ocoteine N-oxide (4), and (+)-leucoxine (5). Third-stage larvae derived from the standard cross with wing cell markers mwh and/or flr(3) were treated chronically. The frequencies of mutant spots observed in marked heterozygous descendants revealed significant dose-dependent genotoxicity for alkaloids 1-4; compounds 1 and 2 were the most active. Alkaloids 1-4 also induced mitotic recombination. The presence of a methoxyl group at C-3 (as in compound 3) lowers its genotoxic effect relative to that of unsubstituted analogue 2, and the introduction of an N-oxide functionality (3 vs. 4) further reduces genotoxicity. The very planar conformation of oxo-aporphine alkaloid 1 may account for its higher genotoxicity vs. its less-planar analogues 3 and 4. As previously reported for (+)-dicentrine (2), alkaloids 1, 3, and 4 may also be DNA intercalating agents, interfering with the catalytic activity of topoisomerases.
authors.affiliation: Universidade Estadual de Mato Grosso do Sul, Unidade Universitária de Mundo Novo - Grupo de Estudo de Ciências Ambientais e Educação (GEAMBE), BR 163 Km 20, 2, Mundo Novo, MS 79980-000, Brazil. Electronic address: zairaguterres@yahoo.com.br.
authors.forename: Zaira da Rosa
authors.initials: Zda R
authors.lastname: Guterres
authors.forename: Ana Francisca Gomes
authors.initials: AF
authors.lastname: da Silva
authors.forename: Walmir Silva
authors.initials: WS
authors.lastname: Garcez
authors.forename: Felipe Rodrigues
authors.initials: FR
authors.lastname: Garcez
authors.forename: Carlos Alexandre
authors.initials: CA
authors.lastname: Fernandes
authors.forename: Fernanda Rodrigues
authors.initials: FR
authors.lastname: Garcez
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D026942:DNA Topoisomerases / Q000378:metabolism; D004331:Drosophila melanogaster / Q000187:drug effects / Q000235:genetics; D007364:Intercalating Agents / Q000737:chemistry / Q000494:pharmacology; D007814:Larva / Q000187:drug effects / Q000235:genetics; D016296:Mutagenesis; D009154:Mutation / Q000235:genetics; D027444:Ocotea / Q000737:chemistry* / Q000235:genetics; D011995:Recombination, Genetic / Q000187:drug effects
chemical_list: D000470:Alkaloids; D007364:Intercalating Agents; D026942:DNA Topoisomerases
keywords: Dicentrine; Homologous recombination; Ocoteine; SMART; Thalicminine