Redox cycling of o-naphthoquinones in trypanosomatids. Superoxide and hydrogen peroxide production.
beta-Lapachone and structurally related lipophilic o-naphthoquinones, namely, CG 8-935, CG 9-442, CG 10-248 and mansonones A, C, E, and F, were investigated for redox cycling, production of reactive oxygen species, and cytotoxicity in the trypanosomatids Crithidia fasciculata and Leptomonas seymouri. Structural analysis of the assayed quinones indicated that a tricyclic structure, including a naphthalene ring, a 1,2b or 1,8bc pyran ring, and two ortho-carbonyl groups were required for quinone activities. The contribution of oxygen radical production to quinone cytotoxicity was supported by: (a) spectroscopic observation of quinone redox cycling; (b) production of the semiquinone radical; (c) H2O2 and O2- production; (d) the effect of beta-lapachone on thiol pools in C. fasciculata; (e) the effect of quinones on cell respiration; (f) superoxide dismutase inactivation after incubation of C. fasciculata with CG 8-935; and (g) the effect of quinones on cell growth.
Molina Portela
M P
MP
Bioenergetics Research Centre, School of Medicine, University of Buenos Aires, Argentina.
Fernandez Villamil
S H
SH
Perissinotti
L J
LJ
Stoppani
A O
AO
D000818:Animals; D016831:Crithidia fasciculata / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006861:Hydrogen Peroxide / Q000378:metabolism*; D009285:Naphthoquinones / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D014351:Trypanosomatina / Q000378:metabolism*
D005609:Free Radicals; D009285:Naphthoquinones; D013438:Sulfhydryl Compounds; D013481:Superoxides; D006861:Hydrogen Peroxide