- Effects of the garlic compounds diallyl sulphide and diallyl disulphide on arylamine N-acetyltransferase activity in Klebsiella pneumoniae
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Arylamine N-acetyltransferase (NAT) activities with 2-aminofluorene (2-AF) were determined in the bacterium Klebsiella pneumoniae. Cytosols or suspensions of K. pneumoniae with or without specific concentrations of diallyl sulphide (DAS) or diallyl disulphide (DADS) as co-treatment showed different percentages of 2-AF acetylation. The data indicated that there was decreased NAT activity associated with increased levels of DAS or DADS in K. pneumoniae. In growth studies on K. pneumoniae it was demonstrated that DAS or DADS elicited a dose-dependent bacteriocide effect on K. pneumoniae. For the cytosol examinations, the apparent values of K(m) and V(max) were 0.96 ± 0.09 mM and 7.87 ± 0.79 nmol min-1 mg-1 protein, respectively, for 2-AF. However, when DAS or DADS was added to the reaction mixtures, the apparent values of K(m) and V(max) were 0.16 ± 0.04 mM and 0.99 ± 0.16 nmol min-1 mg-1 protein with DAS, respectively, and 0.14 ± 0.18 mM and 0.85 ± 0.10 nmol min-1 mg-1 protein with DADS, respectively, for 2-AF. For the intact bacteria examination, the apparent values of K(m) and V(max) were 0.57 ± 0.06 mM and 2.00 ± 0.14 nmol min-1 per 10 x 1010 CFU, respectively, for 2-AF. However, when DAS or DADS was added to the reaction mixtures, the apparent of values of K(m) and V(max) were 0.41 ± 0.04 mM and 1.30 ± 0.10 nmol min-1 per 10 x 1010 CFU with DAS, respectively, and 0.34 ± 0.04 mM and 1.08 ± 0.08 nmol min-1 per 10 x 1010 CFU with DADS, respectively, for 2-AF. This report is the first demonstration to show that the garlic components DAS and DADS would affect K. pneumoniae growth and NAT activity.
- Chen, Guang-Wei,Chung, Jing-Gung,Ho, Heng-Chien,Lin, Juang-Geng
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- Effects of ibuprofen on arylamine N-acetyltransferase activity in human colon tumor cells
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The inhibition of arylamine N-acetyltransferase (NAT) activity by ibuprofen was determined in a human colon tumour (adenocarcinoma) cell line. Two assay systems were employed, one with cellular cytosols (9000 g supernatant) and the other with intact colon tumour cell suspensions. The NAT activity in a human colon tumour cell line was inhibited by ibuprofen in a dose-dependent manner in both systems, i.e. the greater the concentration of ibuprofen in the reaction, the greater the inhibition of NAT activities In both systems. The data also indicated that ibuprofen decreases the apparent K(m) and V(max) of NAT enzyme from human colon tumour cells in both systems examined. This report is the first demonstration to show that ibuprofen affects human colon tumour cell NAT activity.
- Chung, Jing-Gung,Chang, Huei-Ling,Lin, Wen-Chuan,Yeh, Feng-Tsgh,Hung, Chi-Fu
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- Effects of the garlic components diallyl sulfide and diallyl disulfide on arylamine N-acetyltransferase activity in human colon tumour cells
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Diallyl sulfide (DAS) and diallyl disulfide (DADS), major components of garlic, were used to determine inhibition of arylamine N-acetyltransferase (NAT) activity in a human colon tumour (adenocarcinoma) cell line. Two assay systems were performed, one with cellular cytosols (9000 g suprnatant), the other with intact bacterial cell suspensions. The NAT activity in a human colon tumour cell line was inhibited by DAS and DADS in a dose-dependent manner in both system: that is, the greater the concentration of DAS and DADS in the reaction, the greater the inhibition of NAT activities in both systems. The data also indicated that DAS and DADS decrease the apparent values of K(m) and V(max) of NAT enzymes from human colon tumour cells in both systems examined. This is the first report to demonstrate that garlic components do affect human colon tumour cell NAT activity.
- Chen,Chung,Hsieh,Lin
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- The effects of vitamin E on arylamine N-Acetyltransferase activity in strains of Helicobacter pylori from peptic ulcer patients
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Arylamine N-acetyltransferase (NAT) activities with 2-aminofluorene (2-AF) and p-aminobenzoic acid (PABA) were determined in the bacterium Helicobacter pylori. Cytosols or suspensions of H. pylori, with or without specific concentrations of vitamin E co-treatment, showed different percentages of 2-AF acetylation. The data indicated that there was increased NAT activity associated with increased levels of vitamin E in H. pylori cytosols and intact bacteria. For the cytosol and intact bacteria examinations, the apparent values of K(m) and V(max) were increased when vitamin E was added to the reaction mixtures for 2-AF and PABA acetylation, respectively. This report is the first demonstration to show that antioxidant agents (vitamin E) can promote H. pylori N-acetyltransferase activity. Copyright (C) 1999 Elsevier Science Ltd.
- Chung
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- Ibuprofen affects arylamine N-acetyltransferase activity in Helicobacter pylori from peptic ulcer patients
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Arylamine N-acetyltransferase (NAT) activities with 2-aminofluorene and p-aminobenzoic acid were determined in the bacterium Helicobacter pylori collected from peptic ulcer patients. Cytosols or suspensions of H. pylori with or without specific concentrations of ibuprofen co-treatment showed different percentages of 2-aminofluorene and p-aminobenzoic acid acetylation. The data indicate that there was decreased NAT activity associated with increased levels of ibuprofen in H. pylori cytosols. Inhibition of growth studies on H. pylori demonstrated that ibuprofen elicited a dose-dependent bactericide effect in H. pylori cultures, i.e. the greater the concentration of ibuprofen, the greater the inhibition of growth to H. pylori. For the cytosol and intact bacteria examinations, the apparent values of K(m) and V(max) were decreased after co-treatment with 40 μM ibuprofen. This report is the first demonstration of ibuprofen inhibition of arylamine N- acetyltransferase activity and ibuprofen inhibition of growth in the bacterium H. pylori.
- Chang, Shih H.,Chung, Jing G.,Huang, Li J.,Chen, Sheng C.,Kuo, Sheng C.
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- Rhein affects arylamine N-acetyltransferase activity in Helicobacter pylori from peptic ulcer patients
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Arylamine N-acetyltransferase (NAT) activities with 2-aminofluorene and p-aminobenzoic acid were determined in the bacterium Helicobacter pylori collected from peptic ulcer patients. Cytosols or suspensions of H. pylori with or without specific concentrat
- Chung, Jing G.,Tsou, Mei F.,Wang, Hwang H.,Lo, Hsueh H.,Hsieh, Sue E.,Yen, Yee S.,Wu, Lii T.,Chang, Shih H.,Ho, Chin C.,Hung, Chi F.
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- One-step reductive amidation of nitro arenes: Application in the synthesis of Acetaminophen
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A novel thioacetate mediated one-step reductive acetamidation of aryl nitro compounds was developed and applied to an efficient synthesis of acetaminophen. The reaction also proceeds well without a solvent in the presence of a catalytic amount of surfactant.
- Bhattacharya, Apurba,Purohit, Vikram C.,Suarez, Victor,Tichkule, Ritesh,Parmer, Gaurang,Rinaldi, Frank
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p. 1861 - 1864
(2007/10/03)
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- Indium-mediated one-pot reductive conversion of nitroarenes to N-arylacetamides
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N-Arylacetamides were prepared in excellent yields from nitroarenes in the presence of acetic anhydride, acetic acid and indium by a one-pot procedure.
- Kim, Byeong Hyo,Han, Rongbi,Piao, Fengyu,Jun, Young Moo,Baik, Woonphil,Lee, Byung Min
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- DNA adducts from nitroreduction of 2,7-dinitrofluorene, a mammary gland carcinogen, catalyzed by rat liver or mammary gland cytosol
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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.
- Ritter, Clare L.,Culp, Sandra J.,Freeman, James P.,Marques, M. Matilde,Beland, Frederick A.,Malejka-Giganti, Danuta
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p. 536 - 544
(2007/10/03)
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- Synthesis of N,O-Diacetylated N-Arylhydroxylamines by Reduction of Nitroaromatics with Zinc and Acetic Anhydride
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Reduction of nitroaromatic compounds with zinc and acetic anhydride in dichloromethane gave N,O-diacetylated N-arylhydroxylamines in good yields under mild conditions.
- Kim, Byeong Hyo,Jun, Young Moo,Suh, Seung Won,Baik, Woonphil,Lee, Byung Min
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- Glycyrrhizic acid inhibits arylamine N-acetyltransferase activity in Klebsiella pneumoniae in vitro
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Glycyrrhizic acid, one of the proposed chemopreventive drugs, was used to inhibit arylamine N-acetyltransferase (NAT) activity in Klebsiella pneumoniae, both in cytosol and intact bacteria. The NAT activity was measured by using high-performance liquid chromatography to assay the amounts of 2-acetyl-aminofluorene and remaining 2-aminofluorene, The NAT activity in K. pneumoniae was inhibited by glycyrrhizic acid in a dose-dependent manner, The cytosol NAT activities were 0.675 ± 0.028 nmol min-1 mg-1 protein for the acetylation of 2-aminofluorene without glycyrrhizic acid and 0.367 ± 0.008 nmol min-1 mg-1 protein with 8 mM glycyrrhizic acid. The NAT activities measured from intact bacteria were 0.308 ± 0.018 nmol min-1 10-10 colony forming units for the acetylation of 2-aminofluorene without glycyrrhizic acid and 0.236 ± 0.005 nmol min-1 10-10 colony forming units in the presence of 8 mM glycyrrhizic acid, The inhibition of NAT activity by glycyrrhizic acid was demonstrated to remain for at least 4 h, The apparent K(m) and V(max) values calculated from cytosol NAT were 1.08 ± 0.05 mM and 9.09 ± 0.11 nmol min-1 mg-1 protein, respectively, for a-aminofluorene. In the presence of 8 mM glycyrrhizic acid, the apparent K(m) and V(max) values were 0.15 ± 0.01 mM and 0.95 ± 0.11 nmol min-1 mg-1 protein, respectively, for 2-aminofluorene, In intact bacteria, the apparent K(m) and V(max) values were 1.28 ± 0.48 mM and 4.08 ± 1.06 nmol min-1 10-10 colony forming units, respectively for 2-aminofluorene. However, in the presence of 8 mM glycyrrhizic acid, the apparent K(m) and V(max) values were 0.67 ± 0.09 mM and 1.82 ± 0.37 nmol min-1 10-10 colony forming units, respectively, for 2-aminofluorene, Taking these results together, the NAT activity in K. pneumoniae was inhibited by glycyrrhizic acid both in cytosol and intact bacteria. This study provides the first evidence to demonstrate that glycyrrhizic acid inhibits bacterial NAT activity.
- Lo, Hsueh-Hsia,Yen, Yee-Sang,Hsieh, Sue-Er,Chung, Jing-Gung
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p. 385 - 390
(2007/10/03)
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- Reactions of glutathione with carcinogenic esters of N-arylhydroxamic acids
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The nitrenium ions 7a and 7b derived from hydrolysis of N-(sulfonatooxy)-N-acetyl-2-aminofluorene (1a) and N-(sulfonatooxy)-N-acetyl-4-aminobiphenyl (1b) are trapped by glutathione anion (GS-) with selectivity ratios, k(gs)-/k(s), of 8200 ± 600 M-1 and 300 ± 15 M-1, respectively. Since k(s) is known for both of these ions under our reaction conditions, k(gs)- can be calculated. For 7a, k(gs)- is 6.3 x 108 M-1 s-1, and for 7b, k(gs)- is 1.8 x 109 M-1 s-1. Under physiological conditions (50-100 μM GS-) neither ion would be efficiently trapped by GS-. Some of the GSH adducts isolated in this study (4 from 1a, 11 and 12 from 1b) are not derived from nitrenium ion trapping. They arise from GS- trapping of the quinol imines 8a and 8b, which are the initial products of trapping of 7a and 7b by H2O. This reaction is very efficient at physiological GS- concentrations and could lead to significant GSH depletion in vivo. Although it has been known for some time that quinol imines such as 8a and 8b are major hydrolysis products of carcinogenic esters of N-arylhydroxylamines and N-arylhydroxamic acids, no physiological role has been previously suggested for these materials.
- Novak, Michael,Lin, Jing
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p. 1302 - 1308
(2007/10/03)
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- Nucleophilic Substitution on the Ultimate Hepatacarcinogen N-(Sulfonatooxy)-2-(acetylamino)fluorene by Aromatic Amines
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The kinetics and products of the reactions of the title compound 1 with aniline (5) and N,N-dimethylaniline (6) were investigated in MeOH.Addition of 5 (0.1-0.4 M) to a solution of 1 in MeOD-d4 has no effect on the overall rate of decomposition of 1 but generates a number of adducts (20-24) in moderate to high yield.The yields of all solvolysis products, except the rearranged O-sulfates 18 and 19, are suppressed by the addition of 5.The kinetic and product data are consistent with an SN1 mechanism (Scheme IV) in which 18 and 19 are generated by internal return from a tight ion pair, but all other products are generated by nucleophilic attack on a free nitrenium ion or solvent separated ion pair.The reaction of 6 with 1 shows similar characteristics to that of 5 with the exception that 6 reduces 1 in moderate yield to generate 2-(acetylamino)fluorene (25).This reduction occurs in competition with reaction to generate adducts (26, 27) similar to those obtained with 5.Kinetic and product data indicate that 25 is generated by reaction of 6 with a nitrenium ion intermediate.The differences in the behavior of 5 and 6 may be explained by cyclic voltammetry results which show that 6 is oxidized in MeOH more readily than 5 by about 2.5 kcal/mol.The reaction of 1 with 5 and 6 is considerably different from the rections of the same amines with the N-aryl-O-pivaloylhydroxylamines, which were previously shown to proceed via an SN2 mechanism.This change in mechanism may be attributed, in part, to increased steric hindrance at the nitrogen of 1 due to the N-acetyl group.
- Novak, Michael,Rangappa, Kanchugarakoppal S.
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p. 1285 - 1290
(2007/10/02)
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- The Solvolysis of N-Acetoxy-2-acetylaminofluorene and N-Acetoxy-4-acetylaminobiphenyl: Delicate Balance between Nitrenium Ion Formation and Hydrolysis
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The solvolysis of N-acetoxy-2-acetylaminofluorene in aqueous acetone at neutral pH proceeds exclusively with nitrenium ion formation while under the same conditions, the 4-aminobiphenyl analogue undergoes exclusive acyl-oxygen scission.
- Underwood, Graham R.,Kirsch, Robert B.
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p. 136 - 138
(2007/10/02)
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- Non-specific tritiation of some carcinogenic aromatic amines
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2-Aminofluorene, 4-amino-3-methylbiphenyl, 4-amino-biphenyl and 4-amino-4'-fluorobiphenyl were tritiated by acid catalyzed exchange of the corresponding nitro compounds followed by catalytic reduction. The exchange reactions were carried out by heating the nitro compounds in [3H]-trifluoroacetic acid with a catalytic amount of trifluoromethanesulphonic acid (TFMS). No loss of tritium could be detected during the conversion of the tritiated nitro compounds into the corresponding amines by catalytic hydrogenation. Incorporation into the ortho position is very low (4%). During the metabolic activation and binding of the tritiated N-acetyl-2-aminofluorene to rat liver DNA in vivo, no tritium exchange occurred.
- Breeman,Kaspersen,Westra
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p. 741 - 750,748,749
(2007/10/05)
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