Abstract：
:The preparation and DNA binding characteristics of a structural analog of Hoechst 33258 bearing two pyridinic nitrogen atoms are described. The 1H NMR signals of the complex formed between the new ligand 1 and decadeoxyribonucleotide d(CATGGCCATG)2 were assigned by employing one- and two-dimensional NMR techniques. Intermolecular nuclear Overhauser effects (NOE) between the ligand and the DNA receptor fragment confirm that the ligand binds in the minor groove of the DNA, interacting with the centrally located 5'-GGCCA segment. In contrast to the steric clash between the benzimidazole rings of the parent Hoechst 33258 molecule and the guanine 2-NH2 groups, which renders it G.C avoiding and thus A.T base pair preferring, the ligand 1 described here overcomes these unfavorable interactions and instead exhibits a marked preference of G.C base pairs. This behavior appears to arise from additional stabilization due to H-bonding with the guanine 2-NH2 groups. Although a ligand-induced distortion at the binding site is qualitatively assessable, the overall B-type conformation of the DNA fragment is retained upon complexation. The structural conclusions drawn from the NOE-NMR evidence were confirmed by molecular mechanics and molecular modeling studies.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Singh MP,Joseph T,Kumar S,Bathini Y,Lown JWdoi
10.1021/tx00029a003subject
Has Abstractpub_date
1992-09-01 00:00:00pages
597-607issue
5eissn
0893-228Xissn
1520-5010journal_volume
5pub_type
杂志文章abstract：:The clinically used antitumor antibiotic mitomycin C requires a reductive activation to be converted to a bis-electrophile that forms several covalent adducts with DNA, including an interstrand cross-link which is considered to be the lesion responsible for the cytotoxic effects of the drug. Enzymes such as cytochrome...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx9002758
更新日期：2009-10-01 00:00:00
abstract：:Hydrazyl radical intermediates have been suggested as important intermediates in the biochemistry of hydrazides and hydrazines. Although spin-trapping studies have intercepted those species previously, there has been no report of the direct observation of the unstable hydrazyl radicals of isoniazid and iproniazid. We ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx0341759
更新日期：2004-02-01 00:00:00
abstract：:The process of disinfecting drinking water inadvertently leads to the formation of numerous disinfection byproducts (DBPs). Some of these are mutagenic, genotoxic, teratogenic, and cytotoxic, as well as potentially carcinogenic both in vivo and in vitro. We investigated the in vitro biological activity of five DBPs: t...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.5b00283
更新日期：2015-10-19 00:00:00
abstract：:Methylglyoxal is a mutagenic bis-electrophile that is produced endogenously from carbohydrate precursors. Methylglyoxal has been reported to induce DNA-protein cross-links (DPCs) in vitro and in cultured cells. Previous work suggests that these cross-links are formed between guanine and either lysine or cysteine side ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx500068v
更新日期：2014-06-16 00:00:00
abstract：:Increasing exposure of biological systems to large amounts of polycyclic aromatic hydrocarbons is of great public concern. Organisms have an array of biological defense mechanisms, and it is believed that mucosal gel (which covers the respiratory system, the gastrointestinal tract, etc.) provides an effective chemical...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx100426s
更新日期：2011-03-21 00:00:00
abstract：:The 1-octanol/water partition coefficients of a number of toxic and nontoxic analogues of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were determined using centrifugal partition chromatography (CPC), a novel and effective technique for measuring lipophilicity, and found to be highly correlated with values calc...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00027a008
更新日期：1992-05-01 00:00:00
abstract：:Exposure to both endogenous and exogenous formaldehyde has been established to be carcinogenic, likely by virtue of forming nucleic acid and proteins adducts such as N6-formyllysine. To better assess N6-formyllysine as a biomarker of formaldehyde exposure, we studied accumulation of N6-formyllysine adducts in tissues ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.7b00075
更新日期：2017-08-21 00:00:00
abstract：:A new and efficient method is described for the synthesis in gram quantities of the benzo[a]pyrene (B[a]P) metabolic adducts of 2'-deoxyguanosine (dG) and 2'-deoxyadenosine (dA) substituted, respectively, at the N(2)- and N(6)- positions. When the racemic form of the tris(benzoyloxy)amine 5 (related to the notoriously...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx0256174
更新日期：2002-12-01 00:00:00
abstract：:The diarrhetic shellfish toxin composition in the digestive glands of mussels collected in June 2001 from the Northern Adriatic sea was investigated by high-performance liquid chromatography coupled with electrospray ion trap mass spectrometry. Along with known yessotoxins (1, 3-6), identified by comparison of their r...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx025527z
更新日期：2002-07-01 00:00:00
abstract：:Derivatives of methyl 3-(1-methyl-5-(1-methyl-5-(propylcarbamoyl)-1H-pyrrol-3-ylcarbamoyl)-1H-pyrrol-3-ylamino)-3-oxopropane-1-sulfonate (1), a peptide-based DNA minor groove binding methylating agent, were synthesized and characterized. In all cases, the N-terminus was appended with an O-methyl sulfonate ester, while...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx300437x
更新日期：2013-01-18 00:00:00
abstract：:We propose here a combined gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS) metabolic profiling strategy to elucidate the toxicity in rats induced by orally administered multiglycosides of Tripterygium wilfordii Hook. f. (GTW) in multiple organs including the kidney, liv...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx7002905
更新日期：2008-02-01 00:00:00
abstract：:Glutathione peroxidases and their mimics, e.g., ebselen or diaryl tellurides, efficiently reduce peroxynitrite/peroxynitrous acid (ONOO-/ONOOH) to nitrite and protect against oxidation and nitration reactions. Here, we report the second-order rate constant for the reaction of the reduced form of glutathione peroxidase...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx980086y
更新日期：1998-12-01 00:00:00
abstract：:Organic electrophiles have been recognized as important components of the exposome that can be characterized as cumulative totality of exposure in the organism in response to environmental perturbation. For such compounds, chemical reactivity may contribute significantly to the toxicological profile through covalent a...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.5b00398
更新日期：2016-06-20 00:00:00
abstract：:Electrophilic DNA adducts produced following oxidative stress can form DNA-protein cross-links (DPCs), dramatically altering genomic maintenance pathways. Complete characterization of DPCs has been hindered, in part, because of a lack of comprehensive techniques for their analysis. We have, therefore, established a pr...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx400384e
更新日期：2014-01-21 00:00:00
abstract：:1-{4-[(4-Phenyl-5-trifluoromethyl-2-thienyl)methoxy]benzyl}azetidine-3-carboxylic acid (MRL-A) is a potent sphingosine-1-phosphate-1 receptor agonist, with potential application as an immunosuppressant in organ transplantation or for the treatment of autoimmune diseases. When administered orally to rats, radiolabeled ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx300017s
更新日期：2012-07-16 00:00:00
abstract：:It is vital that methylated trivalent arsenicals [MA(III) and DMA(III)] are described and characterized unequivocally due to their high toxicity. Two different ways of generating the methylated trivalent arsenicals have been practiced-reduction of the methylated pentavalent arsenical either by the sodium-metabisulfite...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx049978q
更新日期：2004-08-01 00:00:00
abstract：:Induction of Phase II enzymes of the [Ah] gene battery by L-buthionine (S,R)-sulfoximine (BSO) and other agents was examined in mouse hepatoma Hepa-1c1c7 cells. BSO, a nonelectrophilic inhibitor of gamma-glutamylcysteine synthetase (GCS), is routinely used to examine the toxicological implications of GSH depletion. Ex...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00045a015
更新日期：1995-04-01 00:00:00
abstract：:The activity of three metabolically activated methylating agents, N-methyl-N-(acetoxymethyl)nitrosamine (DMN-OAc), methylnitrosourethane (MNUT), and (methylazoxy)methanol acetate (MAM-Ac), were determined in cell culture by using a P388 cell growth rate inhibition assay. Experiments were conducted with normal P388 cel...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00011a004
更新日期：1989-09-01 00:00:00
abstract：:meso-2,3-Dimercaptosuccinic acid is an orally active chelating agent useful for the treatment of lead intoxication. Since it is believed to be extracellular in its distribution, analogs have been synthesized in a search for one that will enter the cell and successfully complete for firmly bound intracellular toxic hea...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00032a010
更新日期：1993-03-01 00:00:00
abstract：:A series of tether-linked bis netropsins have been synthesized in order to assess the phasing problem, which arises because of the lack of dimensional correspondence between oligopeptides and oligonucleotides in DNA binding characteristics. The consequences of incorporating variable-length flexible and rigid tethers [...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00014a013
更新日期：1990-03-01 00:00:00
abstract：:Protein glutathionylation is an important protein post-translational modification associated with oxidative stress, in which the thiol groups of cysteine residues react with glutathione and form disulfide bonds. Glutathionylation has been shown to affect protein structure and modulate protein function, and is implicat...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx5000359
更新日期：2014-05-19 00:00:00
abstract：:The urine from mice exposed to styrene vapors (600 and 1200 mg/m(3), 6 h) was analyzed for ring-oxidized metabolites of styrene. To facilitate the identification of metabolites in urine, the following potential metabolites were prepared: 2-, 3-, and 4-vinylphenol (2-, 3-, and 4-VP), 4-vinylpyrocatechol, and 2-, 3-, an...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx9004192
更新日期：2010-01-01 00:00:00
abstract：:Raloxifene is a selective estrogen receptor modulator which is effective in the treatment of osteoporosis in postmenopausal women. We report herein that cytochrome P450 (P450)3A4 is inhibited by raloxifene in human liver microsomal incubations. The nature of the inhibition was irreversible and was NADPH- and preincuba...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx0200109
更新日期：2002-07-01 00:00:00
abstract：:Hydrophobic and volatile chemicals have proven to be difficult to dose in cell assays. Cosolvents are often needed to dissolve these chemicals in cell culture medium. Moreover, the free concentration of these chemicals in culture medium may diminish over time due to metabolism, evaporation, and nonspecific binding to ...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx1002595
更新日期：2010-11-15 00:00:00
abstract：:The crystal structure of the food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) has been determined by single-crystal X-ray crystallography. Crystals grown by evaporation of an aqueous solution form in the monoclinic space group P2(1)/n with two molecules of PhIP per asymmetric unit, along with six w...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx950168b
更新日期：1996-04-01 00:00:00
abstract：:For decades, many studies have linked maternal smoking to an increased risk of preterm birth. As a result, the scientific community has long hypothesized that exposure to environmental tobacco smoke (ETS), commonly referred to as second-hand smoke, is also associated with an increased risk of preterm birth. Multiple s...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/acs.chemrestox.7b00054
更新日期：2017-07-17 00:00:00
abstract：:The efficacy of 3-tert-butyl-4-hydroxyanisole (BHA) as a chemopreventive agent against chemically induced cancer or toxicity may involve the direct modulation of cytochrome P-450 dependent monooxygenase function. This hypothesis was investigated by using purified rabbit cytochrome P-450IA2 and P-450IIB4 in a reconstit...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx00021a004
更新日期：1991-05-01 00:00:00
abstract：:Exposure to aristolochic acid I (AAI) is associated with aristolochic acid nephropathy, Balkan endemic nephropathy, and urothelial cancer. Individual differences in xenobiotic-metabolizing enzyme activities are likely to be a reason for interindividual susceptibility to AA-induced disease. We evaluated the reductive a...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx200259y
更新日期：2011-10-17 00:00:00
abstract：:Tetrandrine, a bisbenzylisoquinoline alkaloid, has demonstrated promising pharmacologic activities. The alkaloid has a great potential for clinical use, so a careful, thorough toxicity evaluation of the alkaloid is required. In the present study, 24 h acute toxicity of tetrandrine was evaluated in CD-1 mice. Single in...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx200290s
更新日期：2011-12-19 00:00:00
abstract：:3-(2-Deoxy-beta-D-erythro-pentofuranosyl)-6-hydroxy-5,6,7,8-tetrahydropyrimido[1,2-a]purin-10(3H)-one is formed in low yield by the reaction of acrolein with 2'-deoxyguanosine. The nucleoside and an oligodeoxynucleotide containing it have been synthesized. For preparation of the nucleoside 2'-deoxyguanosine was alkyla...
journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx010181y
更新日期：2002-05-01 00:00:00
