Mpm. Portela et al., REDOX CYCLING OF O-NAPHTHOQUINONES IN TRYPANOSOMATIDS - SUPEROXIDE AND HYDROGEN-PEROXIDE PRODUCTION, Biochemical pharmacology, 52(12), 1996, pp. 1875-1882
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, w
ere investigated for redox cycling, production of reactive oxygen spec
ies, and cytotoxicity in the trypanosomatids Crithidia fasciculata and
Leptomonas seymouri. Structural analysis of the assayed quinones indi
cated 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 q
uinone cytotoxicity was supported by: (a) spectroscopic observation of
quinone redox cycling; (b) production of the semiquinone radical; (c)
H,O, and O-2(-) production; (d) the effect of beta-lapachone on thiol
pools in C. fasciculata; (e) the effect of quinones on cell respirati
on; (f) superoxide dismutase inactivation after incubation of C. fasci
culata with CG 8-935; and (g) the effect of quinones on cell growth. C
opyright (C) 1996 Elsevier Science Inc.