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.
Miskiniene
V
V
Institute of Biochemistry, Vilnius, Lithuania.
Dickancaite
E
E
Nemeikaite
A
A
Cenas
N
N
D000818:Animals; D001388:Aziridines / Q000494:pharmacology; D001728:Dicumarol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005287:Ferredoxin-NADP Reductase / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000821:virology; D005663:Furans / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D007668:Kidney / Q000166:cytology / Q000821:virology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D042844:L-Lactate Dehydrogenase (Cytochrome); D001909:Leukemia Virus, Bovine / Q000235:genetics; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D009574:Nitro Compounds / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology*; D009579:Nitrobenzoates / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D009582:Nitrofurantoin / Q000494:pharmacology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D013379:Substrate Specificity; D018675:Toxicity Tests; D014315:Triterpenes / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology*; D000094062:Betulinic Acid
D001388:Aziridines; D001728:Dicumarol; D005287:Ferredoxin-NADP Reductase; D005663:Furans; D007770:L-Lactate Dehydrogenase; D042844:L-Lactate Dehydrogenase (Cytochrome); D016660:NAD(P)H Dehydrogenase (Quinone); D009574:Nitro Compounds; D009579:Nitrobenzoates; D009582:Nitrofurantoin; D014315:Triterpenes; C108342:betulin-(28)-5'-(aziridin-1-yl)-2',4'-dinitrobenzoate; D000094062:Betulinic Acid; C108343:betulin-(28)-5'-nitro-2'-furoate; C002503:betulin; C100099:tretazicar