title: [Effect of naphthoquinone-imines on the production of hydrogen peroxide by Crithidia fasciculata and Leptomonas seymouri].
abstract: It has been synthesized a series of 4-aminoisoxazol-1,2-naftoquinones, which inhibit growth and DNA synthesis in Trypanosoma cruzi. This effect was related to quinone induction of oxyradical generation. N-(5-methyl-3-isoxazolyl)-4-amino-1,2-naftoquinone and 2-hydroxy-N-(3,5-dimethyl-1-4-isoxazolyl)-1,4-naftoquinone-4 -imine inhibited also growth of Crithidia fasciculata and Leptomonas symouri, two organisms that may prove useful for the assay of trypanocidal drugs. In order to establish the role of oxyradicals for quinone-imine toxicity, the latter redox-cycling was demonstrated by a) reversible change in their spectra; b) reduction under anaerobic conditions, and c) quinol oxidation by oxygen. Production of H2O2, measured by the microperoxidase method, was maximal with N-(5-methyl-3-isoxazolyl)-4-amine-1,2-naftoquinone (IVD) (0.29-0.26 nmol/min/mg of cell protein), either with C. fasciculata or L. seymouri. Lesser, though significant activities were obtained with 2-hydroxy-N-(5-methyl-3-isoxazolyl)-1,4-naftoquinone-4-imine (IIID) and 2-hydroxy-N-(3-methyl-5-isoxazolyl)-1,4-naftoquinone-4-imine (IIIE) whereas IIIA and IIIC were inactive. O2-. generation, measured by the adrenochrome method, was induced by naftoquinone-imines with a hydroxyl group at C-2 (IIIE, 2-hydroxy-N-(3,5-dimethyl-4-isoxazolyl)-1,4-naftoquinone-4-i mine (IIIC) and 2-hydroxy-N-(3,4-dimethyl-5-isoxazolyl)-1,4-naftoquinone-4-i mine (IIIA), but no by IVD, with a carbonyl group at C-2. Measurement of catalase and superoxide dismutase in both organisms yielded significant activities, but ascorbate peroxidase, guaiacol peroxidase and bencidine peroxidase were inactive.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Centro de Investigaciones Bioenergéticas, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
authors.forename: M P
authors.initials: MP
authors.lastname: Molina Portela
authors.forename: A O
authors.initials: AO
authors.lastname: Stoppani
mesh_terms: D000818:Animals; D003421:Crithidia / Q000187:drug effects / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007097:Imines / Q000494:pharmacology; D009285:Naphthoquinones / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism; D014351:Trypanosomatina / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D007097:Imines; D009285:Naphthoquinones; D013481:Superoxides; D006861:Hydrogen Peroxide
vernacular_title: Influencia de naftoquinona-iminas sobre la producción de peróxido de hidrógeno por Crithidia fasciculata y Leptomonas seymouri.