1214-32-0Relevant articles and documents
Synthesis of Alkylated Aminofluorenes by Palladium-Catalyzed Substitution at Halofluorenes
Saroja, Ginagunta,Pingzhu, Zhang,Ernsting, Nikolaus P.,Liebscher, Juergen
, p. 987 - 990 (2004)
New N-substituted 2-amino-9,9-dialkylfluorenes optionally bearing electron-withdrawing substituents such as nitro or cyano in position 7 can be synthesized starting from 2-halo-9,9-dialkylfluorenes by Pd-catalyzed substitution with amines. Chiral amino groups can be introduced by this method too. 2-N,N-Dimethylamino-7-nitro-9H-fluorene was obtained in a convenient way by reductive amination. The N-substituted 2-amino-7-nitro-9H-fluorenes are promising candidates for fluorescence probes for femtosecond solvation dynamics.
Preneoplastic lesions, DNA adduct formation and mutagenicity of 5-, 7- and 9 -hydroxy-2-nitrofluorene, metabolites of the air pollutant 2-nitrofluorene
Cui, Xian-Shu,Bergman, Jan,Moeller, Lennart
, p. 147 - 155 (1996)
The metabolites of 2-nitrofluorene (NF), 5-, 7- and 9-OH-2-nitrofluorene (OH-NF) were compared for their genotoxicity. Seventy-two hours after intraperitoneal administration of these substances individually to rats (100 mg/kg body wt.), DNA adducts in liver tissue were analyzed with 32P-TLC and 32P-HPLC. An in vivo liver model was used to test the initiating capacity of the said substances for the formation of preneoplastic lesions. 5-OH-NF showed low capacity to induce DNA adduct formation and low potential as initiator to induce preneoplastic lesions-foci/nodules in the liver of rats. Both 7- and 9-OH-NF induced DNA adducts and preneoplastic liver lesions but with smaller quantities compared to NF. It seems that 7- and 9-OH-NF can not be considered as detoxification products of NF. In general, the initiating capacity of these substances for the formation of preneoplastic lesions has a good correlation with their potency to form DNA adducts.
DNA adducts from nitroreduction of 2,7-dinitrofluorene, a mammary gland carcinogen, catalyzed by rat liver or mammary gland cytosol
Ritter, Clare L.,Culp, Sandra J.,Freeman, James P.,Marques, M. Matilde,Beland, Frederick A.,Malejka-Giganti, Danuta
, p. 536 - 544 (2002)
Nitrofluorenes are mutagenic and carcinogenic environmental pollutants arising chiefly from combustion of fossil fuels. Nitro aromatic compounds undergo nitroreduction to N-hydroxy arylamines that bind to DNA directly or after O-esterification. This study analyzes the DNA binding and adducts from the in vitro nitroreduction of 2,7-dinitrofluorene (2,7-diNF), a potent mammary carcinogen in the rat. Potential adduct(s) of 2,7-diNF was (were) generated by reduction of 2-nitroso-7-NF with ascorbate/H+ in the presence of calf thymus DNA. The major adduct was characterized by HPLC/ESI/MS and 1H NMR spectrometry as N-(deoxyguanosin-8-yl)-2-amino-7-NF, and a minor one was determined by HPLC/ESI/MS to be a deoxyadenosine adduct of 2-amino-7-NF. Products from enzymatic nitroreduction were monitored by HPLC and DNA adduct formation by 32P-postlabeling. Xanthine oxidase/hypoxanthine-catalyzed nitroreduction of 2,7-diNF, 2-nitrofluorene (2-NF), and 1-nitropyrene (1-NP) yielded the respective amines to similar extents (30-50%). However, the level of the major adducts (～0.15/106 nucleotides) from 2-NF [N-(deoxyguanosin-8-yl)-2-aminofluorene] and 2,7-diNF [N-(deoxyguanosin-8-yl)-2-amino-7-NF] was ≤2% that from 1-NP. In the presence of acetyl CoA, nitroreduction of 2-NF catalyzed by rat liver cytosol/NADH yielded the same adduct at a level of 2.2/106 nucleotides. Liver or mammary gland cytosol with acetyl CoA yielded mainly N-(deoxyguanosin-8-yl)-2-amino-7-NF from 2,7-diNF at >30 adducts/106 nucleotides, levels comparable to those from 1,6-dinitropyrene and 4- or 49-fold greater than the respective levels without acetyl CoA. Recovery of 2-nitroso-7-NF and 2-amino-7-NF from cytosol-catalyzed reduction of 2,7-diNF indicated nitroreduction and an N-hydroxy arylamine intermediate. Likewise, the presence of 2-acetylamino-7-NF indicated that reactivity with acyltransferase(s) was not prevented by the nitro group at C7. These data are consistent with activation of 2,7-diNF via nitroreduction to the N-hydroxy arylamine and acetyl CoA-dependent O-acetylation of the latter to bind to DNA. Enzymatic nitroreduction of 2,7-diNF was greatly enhanced by 9-oxidation. The nitroreduction of either 9-oxo-2,7-diNF or 9-hydroxy-2,7-diNF catalyzed by liver cytosol with acetyl CoA yielded two adducts (>2/106 nucleotides). Differences in the TLC migration of these adducts, compared to those from 2,7-diNF, and the lack of 2,7-diNF formation in the incubations suggested retention of the C9-oxidized groups. The relative ratios of the amine to amide from nitroreductions of 9-oxo-2,7-diNF and 2,7-diNF catalyzed by liver cytosol suggested that the 9-oxo group decreased reactivity with acyltransferase and, thus, the amount of N-acetoxy arylamine that binds to DNA. The mammary gland tumorigenicity of 2,7-diNF and the extent of its activation by the tumor target tissue shown herein suggest relevance of this environmental pollutant for breast cancer.
