Nitroaromatic betulin derivatives as redox cycling agents.

We have synthesized nitroaromatic derivatives of triterpenoid betulin (lup-20(29)-ene-3 beta, 28-diol), betulin-(28)-5'-(aziridin-1-yl)-2',4'-dinitrobenzoate and betulin-(28)-5'-nitro-2'-furoate. These compounds were reduced in single-electron way by ferredoxin: NADP+ reductase and flavocytochrome b2 at rates comparable with their simple structure analogs. Besides, these compounds were substrates for DT-diaphorase. Their toxicity to bovine leukemia virus-transformed lamb fibroblast culture was partly prevented by antioxidant N,N'-diphenyl-p-phenylene diamine and desferrioxamine, indicating an involvement of oxidative stress in their cytotoxicity.