Docampo R, Moreno S N
Fed Proc. 1986 Sep;45(10):2471-6.
In recent years it has been apparent that many of the known antiparasitic drugs produce free radicals. Intracellular reduction followed by autooxidation yielding O.-2 and H2O2 has been suggested as the mode of action of nifurtimox on Trypanosoma cruzi and as the basis of its toxicity in mammals. On the other hand, free radical intermediates that do not generate oxygen-reduction products under physiological conditions have been found in the metabolic pathways of other antiparasitic nitro compounds (benznidazole, metronidazole, and other 5-nitroimidazoles) used in the treatment of diseases such as Chagas' disease, trichomoniasis, giardiasis, balantidiasis, amebiasis, and schistosomiasis. In these cases, as well as in the case of niridazole (used in the treatment of schistosomiasis), covalent binding or other interactions of the intermediates of nitroreduction with parasite macromolecules are possibly involved in their toxicity. Redox cycling of these compounds under aerobic conditions appears to be a detoxification reaction by inhibiting net reduction of the drugs.
近年来，很明显许多已知的抗寄生虫药物会产生自由基。细胞内还原随后自动氧化产生超氧阴离子（O₂⁻）和过氧化氢（H₂O₂），这被认为是硝呋莫司对克氏锥虫的作用方式及其在哺乳动物中产生毒性的基础。另一方面，在用于治疗恰加斯病、滴虫病、贾第虫病、小袋虫病、阿米巴病和血吸虫病等疾病的其他抗寄生虫硝基化合物（苯硝唑、甲硝唑和其他5-硝基咪唑）的代谢途径中，发现了在生理条件下不会产生氧还原产物的自由基中间体。在这些情况下，以及在硝咪唑（用于治疗血吸虫病）的情况下，硝基还原中间体与寄生虫大分子的共价结合或其他相互作用可能涉及其毒性。这些化合物在有氧条件下的氧化还原循环似乎是一种解毒反应，通过抑制药物的净还原。
