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...

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Bibliographic Details
Published in:Biochemical pharmacology 1996-12, Vol.52 (12), p.1875-1882
Main Authors: MOLINA PORTELA, M. P, FERNANDEZ VILLAMIL, S. H, PERISSINOTTI, L. J, STOPPANI, A. O. M
Format: Article
Language:English
Subjects:
Animals
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antiparasitic agents
Biological and medical sciences
Crithidia fasciculata - metabolism
Electron Spin Resonance Spectroscopy
Free Radicals
Hydrogen Peroxide - metabolism
Medical sciences
Naphthoquinones - metabolism
Oxidation-Reduction
Oxygen Consumption
Pharmacology. Drug treatments
Sulfhydryl Compounds - metabolism
Superoxides - metabolism
Trypanosomatina - metabolism
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Summary: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.
ISSN:0006-2952
1873-2968
DOI:10.1016/S0006-2952(96)00601-6