Gorla N, Díaz Gómez M I, Castro J A
Arch Int Pharmacodyn Ther. 1986 Mar;280(1):22-31.
Benznidazole (Bz) (N-benzyl-2-nitro-1-imidazole acetamide) is one of the drugs used in the chemotherapy of Chagas' disease. Microsomal suspensions anaerobically activated Bz in the presence or absence of NADPH to metabolites that covalently bind to proteins or to DNA incorporated into the incubation mixture. At high Bz concentrations (0.2 mM) NADPH enhanced the intensity of the process while at low Bz concentrations (0.02 mM) it decreased it. Nuclear preparations were also able to anaerobically activate Bz to reactive metabolites that bind covalently their DNA and proteins. The process was enzymatic and required NADPH. Most of the interaction between Bz metabolites and nuclear proteins involved the acidic non-histone proteins and those from the nuclear sap. A minor part of the interaction was with basic deoxyribonucleoproteins, acidic ribonucleoproteins and residual fractions. Almost no interaction with histones was observed. Potential toxicological implications of the observed interactions are analyzed.
苯硝唑（Bz）（N-苄基-2-硝基-1-咪唑乙酰胺）是用于恰加斯病化疗的药物之一。微粒体悬浮液在有或没有NADPH的情况下将Bz厌氧激活为与蛋白质或与孵育混合物中掺入的DNA共价结合的代谢产物。在高Bz浓度（0.2 mM）下，NADPH增强了该过程的强度，而在低Bz浓度（0.02 mM）下则降低了该强度。细胞核制剂也能够将Bz厌氧激活为与它们的DNA和蛋白质共价结合的反应性代谢产物。该过程是酶促的，需要NADPH。Bz代谢产物与核蛋白之间的大多数相互作用涉及酸性非组蛋白和来自核液的蛋白。相互作用的一小部分是与碱性脱氧核糖核蛋白、酸性核糖核蛋白和残留部分。几乎未观察到与组蛋白的相互作用。分析了所观察到的相互作用的潜在毒理学意义。
