Large-scale synthesis of the catechol metabolites of diethylstilbestrol and hexestrol.

Abstract:

:Diethylstilbestrol (DES) and hexestrol (HES) are carcinogenic synthetic estrogens. The major metabolites of these compounds are their catechol derivatives, 3'-OH-DES and 3'-OH-HES. Oxidation of these metabolites leads to the electrophilic quinones, which are presumably involved in the tumor-initiating process. A synthetic route based on the McMurry coupling reaction was developed for the synthesis of 3'-OH-DES. Using commercially inexpensive starting materials, this compound was synthesized in four steps, and the cis and trans isomers were separated and identified. Following the same synthetic route, 3'-OH-HES was synthesized in five steps.

journal_name

Chem Res Toxicol

authors

Jan ST,Rogan EG,Cavalieri EL

doi

10.1021/tx970140v

subject

Has Abstract

pub_date

1998-05-01 00:00:00

pages

408-11

issue

5

eissn

0893-228X

issn

1520-5010

pii

tx970140v

journal_volume

11

pub_type

杂志文章
  • Chemical analysis and hemolytic activity of the fava bean aglycon divicine.

    abstract::Divicine is an unstable aglycon metabolite of the fava bean pyrimidine beta-glucoside vicine. Divicine has long been thought to be a mediator of an acute hemolytic crisis, known as favism, in susceptible individuals who ingest fava beans (Vicia faba). However, a recent report has questioned the chemical identity of th...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx00034a009

    authors: McMillan DC,Schey KL,Meier GP,Jollow DJ

    更新日期:1993-07-01 00:00:00

  • Molecular recognition between oligopeptides and nucleic acids: DNA binding selectivity of a series of 1,2,4-triazole-containing lexitropsins.

    abstract::The synthesis of a series of 1,2,4-triazole-containing oligopeptide lexitropsins related to the natural antitumor antibiotic distamycin is described. The binding properties of these new agents to both native DNAs and synthetic polydeoxyribonucleotides were determined by UV absorption and circular dichroism studies. Th...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx00020a019

    authors: Rao KE,Krowicki K,Burckhardt G,Zimmer C,Lown JW

    更新日期:1991-03-01 00:00:00

  • Role of metallothionein in zinc(II) and chromium(III) mediated tolerance to carbon tetrachloride hepatotoxicity: evidence against a trichloromethyl radical-scavenging mechanism.

    abstract::The .CCl3 radical generated during the metabolism of CCl4 is readily spin trapped in vivo and in vitro by phenyl N-tert-butylnitrone (PBN) to form the stable PBN/.CCl3 radical adduct, which can then be extracted into organic solvents and detected by ESR spectroscopy. We have used this technique to examine the proposed...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx00035a017

    authors: Hanna PM,Kadiiska MB,Jordan SJ,Mason RP

    更新日期:1993-09-01 00:00:00

  • Pristine (C60) and hydroxylated [C60(OH)24] fullerene phototoxicity towards HaCaT keratinocytes: type I vs type II mechanisms.

    abstract::The increasing use of fullerene nanomaterials has prompted widespread concern over their biological effects. Herein, we have studied the phototoxicity of gamma-cyclodextrin bicapped pristine C 60 [(gamma-CyD) 2/C 60] and its water-soluble derivative C 60(OH) 24 toward human keratinocytes. Our results demonstrated that...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx800056w

    authors: Zhao B,He YY,Bilski PJ,Chignell CF

    更新日期:2008-05-01 00:00:00

  • Intracellular activation of cytotoxic agents: kinetic models for methylnitrosoureas and N-methyl-N'-nitro-N-nitrosoguanidine in cell culture.

    abstract::The cytotoxic activity of N-methyl-N-nitrosourea (MNU), streptozotocin, and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was determined in cell culture by using a P388 cell growth rate inhibition assay. These agents appear to have very different activities when inhibition is related to the agent concentration in the cu...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx00009a006

    authors: Weinkam RJ,Dolan ME

    更新日期:1989-05-01 00:00:00

  • A study of inactivation reactions of N-acetylcysteine with mucochloric acid, a mutagenic product of the chlorination of humic substances in water.

    abstract::The Salmonella typhimurium (TA100) mutagenic compound, mucochloric acid [3,4-dichloro-5-hydroxy-2(5H)-furanone (MCA)], was inactivated by in vitro N-acetylcysteine (NAC). The reaction of MCA with NAC at pH7 was second order and gave products 4, 5, and 6a that resulted from the displacement of chlorine from C-3 or C-4 ...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx00029a005

    authors: LaLonde RT,Xie S

    更新日期:1992-09-01 00:00:00

  • In Vitro Cytotoxicity and Adaptive Stress Responses to Selected Haloacetic Acid and Halobenzoquinone Water Disinfection Byproducts.

    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

    authors: Procházka E,Escher BI,Plewa MJ,Leusch FD

    更新日期:2015-10-19 00:00:00

  • Pulmonary toxicity and metabolic activation of tetrandrine in CD-1 mice.

    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

    authors: Jin H,Li L,Zhong D,Liu J,Chen X,Zheng J

    更新日期:2011-12-19 00:00:00

  • Lauric acid as a model substrate for the simultaneous determination of cytochrome P450 2E1 and 4A in hepatic microsomes.

    abstract::In vitro techniques have been utilized to investigate the microsomal enzymes involved in the metabolism of lauric acid and to establish conditions in which it can be used as a model substrate for both cytochrome P450 4A and cytochrome P450 2E1 in human liver microsomes. Studies of enzyme kinetics of lauric acid omega-...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx00042a018

    authors: Clarke SE,Baldwin SJ,Bloomer JC,Ayrton AD,Sozio RS,Chenery RJ

    更新日期:1994-11-01 00:00:00

  • Interaction of trivalent arsenicals with metallothionein.

    abstract::Arsenic is a human carcinogen, causing skin, bladder, and lung cancers. Although arsenic in drinking water affects millions of people worldwide, the mechanism(s) of action by which arsenic causes cancers is not known. Arsenic probably exerts some toxic effects by binding with proteins. However, few experimental data a...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx034053g

    authors: Jiang G,Gong Z,Li XF,Cullen WR,Le XC

    更新日期:2003-07-01 00:00:00

  • A new role for glutathione: protection of vitamin B12 from depletion by xenobiotics.

    abstract::NADPH in microsomes reduces the hydroxocob(III)alamin form of vitamin B12 to cob(II)alamin and the supernucleophilic cob(I)alamin, which are both highly reactive toward xenobiotic epoxides formed by mammalian metabolism of dienes such as the industrially important chemicals chloroprene and 1,3-butadiene. With styrene,...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx0497898

    authors: Watson WP,Munter T,Golding BT

    更新日期:2004-12-01 00:00:00

  • Metabolism and disposition of O6-benzyl-2'-deoxyguanosine in Sprague-Dawley rats.

    abstract::O6-Benzyl-2'-deoxyguanosine is a potential antitumor drug modulator that is intended to reduce or eliminate O6-alkylguanine-DNA alkyltransferase activity in tumors prior to treatment with genotoxic chemotherapeutic alkylating agents. The rationale for using this compound instead of the more active O6-benzylguanine and...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx00042a008

    authors: Kokkinakis DM,Moschel RC,Pegg AE,Dolan ME,Schold SC Jr

    更新日期:1994-11-01 00:00:00

  • Bezafibrate induces a mitochondrial derangement in human cell lines: a PPAR-independent mechanism for a peroxisome proliferator.

    abstract::Bezafibrate is a hypolipidemic drug that belongs to the group of peroxisome proliferators because it binds to peroxisome proliferator-activated receptors type alpha (PPARs). Peroxisome proliferators produce a myriad of extraperoxisomal effects, which are not necessarily dependent on their interaction with PPARs. An in...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx0341052

    authors: Scatena R,Bottoni P,Vincenzoni F,Messana I,Martorana GE,Nocca G,De Sole P,Maggiano N,Castagnola M,Giardina B

    更新日期:2003-11-01 00:00:00

  • Miscoding by the exocyclic and related DNA adducts 3,N4-etheno-2'-deoxycytidine, 3,N4-ethano-2'-deoxycytidine, and 3-(2-hydroxyethyl)-2'-deoxyuridine.

    abstract::3,N4-Etheno-2'-deoxycytidine, 3-(hydroxyethyl)-2'-deoxyuridine, and 3,N4-ethano-2'-deoxy-cytidine are found in DNA of cells treated with either vinyl chloride or 1,3-bis(2-chloroethyl)-nitrosourea. These exocyclic and related DNA adducts were incorporated into oligodeoxynucleotides, which were then used as templates f...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx00043a021

    authors: Zhang W,Johnson F,Grollman AP,Shibutani S

    更新日期:1995-01-01 00:00:00

  • Dominant contribution of P450 3A4 to the hepatic carcinogenic activation of aflatoxin B1.

    abstract::The hepatic carcinogen aflatoxin B1 (AFB1) is metabolized in the liver by at least four different P450s, all of which exhibit large interindividual differences in the expression levels. These differences could affect the individual risk of hepatocellular carcinoma (HCC). We investigated the metabolism of AFB1 in a pan...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx050358e

    authors: Kamdem LK,Meineke I,Gödtel-Armbrust U,Brockmöller J,Wojnowski L

    更新日期:2006-04-01 00:00:00

  • Dihydroxy-, hydroxyspirolactone-, and dihydroxyspirolactone-urochlorins induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in the liver of mice.

    abstract::Previous work has shown that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes porphyria, enhanced by iron, in C57BL/6J mice with marked accumulation in the liver of uroporphyrin I and III isomers and heptacarboxylic acid III and is one model of human porphyria cutanea tarda. Preliminary examination by HPLC also indic...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx060212v

    authors: Lim CK,Danton M,Clothier B,Smith AG

    更新日期:2006-12-01 00:00:00

  • Enhanced bioavailability of polyaromatic hydrocarbons in the form of mucin complexes.

    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

    authors: Drug E,Landesman-Milo D,Belgorodsky B,Ermakov N,Frenkel-Pinter M,Fadeev L,Peer D,Gozin M

    更新日期:2011-03-21 00:00:00

  • Water-soluble organotellurium compounds: catalytic protection against peroxynitrite and release of zinc from metallothionein.

    abstract::The antioxidant properties of a number of water-soluble diorganyl tellurides have been investigated. These organotellurium compounds efficiently protect against peroxynitrite-mediated oxidation of dihydrorhodamine 123, hydroxylation of benzoate, and nitration of 4-hydroxyphenyl acetate. The peroxidation of the zinc st...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx990156g

    authors: Jacob C,Arteel GE,Kanda T,Engman L,Sies H

    更新日期:2000-01-01 00:00:00

  • Carbon Disulfide Induces Embryo Implantation Disorder by Disturbing the Polarization of Macrophages in Mice Uteri.

    abstract::Carbon disulfide (CS2) induces embryo implantation disorders. Macrophages participate in the process of pregnancy. Therefore, we want to explore the effects of CS2 exposure on polarization and immune function of macrophages in pregnant mice uteri. The exposure times were gestation days 3 (GD3), 4 (GD4), and 5 (GD5), a...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/acs.chemrestox.9b00119

    authors: Zhang T,Hu C,Wu Y,Wang S,Liu X,Zhang D,Huang F,Gao H,Wang Z

    更新日期:2019-10-21 00:00:00

  • Atrazine Triggers the Extrinsic Apoptosis Pathway in Lymphocytes of the Frog Pelophylax nigromaculata in Vivo.

    abstract::Atrazine (ATR) is extensively used worldwide as an herbicide, with a global ecological influence. The widespread distribution of herbicides may be one of the possible reasons for the decline in the global amphibian population. The acute toxicity and potential toxicological mechanisms of ATR on the immune system of fro...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/acs.chemrestox.5b00238

    authors: Jia X,Wang D,Gao N,Cao H,Zhang H

    更新日期:2015-10-19 00:00:00

  • Immunotoxicity induced by acute subtoxic doses of paraquat herbicide: implication of shifting cytokine gene expression toward T-helper (T(H))-17 phenotype.

    abstract::Paraquat (PQ) is a free radical-inducing agent commonly used as an herbicide. This study assesses the acute immunotoxicity of PQ in BALB/c mice and examines its effect on cytokine gene expression profile. It was found that single subtoxic oral doses of 2, 4, and 20 mg/kg significantly inhibited the in vitro mitogen-in...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx300194t

    authors: Hassuneh MR,Albini MA,Talib WH

    更新日期:2012-10-15 00:00:00

  • Determination of glycated nucleobases in human urine by a new monoclonal antibody specific for N2-carboxyethyl-2'-deoxyguanosine.

    abstract::Sugars and sugar degradation products react in vivo readily with proteins (glycation) resulting in the formation of a heterogeneous group of reaction products, which are called advanced glycation end products (AGEs). AGEs notably change the structure and function of proteins so that extended protein-AGE formation is l...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx049929d

    authors: Schneider M,Thoss G,Hübner-Parajsz C,Kientsch-Engel R,Stahl P,Pischetsrieder M

    更新日期:2004-10-01 00:00:00

  • DNA adducts of acrolein: site-specific synthesis of an oligodeoxynucleotide containing 6-hydroxy-5,6,7,8-tetrahydropyrimido[1,2-a]purin-10(3H)-one, an acrolein adduct of guanine.

    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

    authors: Nechev LV,Kozekov ID,Brock AK,Rizzo CJ,Harris TM

    更新日期:2002-05-01 00:00:00

  • Synthesis, absolute configuration, and bacterial mutagenicity of the 8 stereoisomeric vicinal diol epoxides at the terminal benzo ring of carcinogenic dibenz[a,h]anthracene.

    abstract::The synthesis of the 8 possible stereoisomeric diol epoxides (DEs) at the terminal benzo ring of carcinogenic dibenz[a,h]anthracene (DBA) is reported. trans-3,4-Dihydroxy-3,4-dihydro-DBA (1) afforded the 4 bay region DEs: the enantiomeric pairs of the anti diastereomers (+)-3/(-)-3 and of the syn diastereomers (-)-4/(...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx200398b

    authors: Frank H,Funk M,Oesch F,Platt KL

    更新日期:2011-12-19 00:00:00

  • Can Galactose Be Converted to Glucose in HepG2 Cells? Improving the in Vitro Mitochondrial Toxicity Assay for the Assessment of Drug Induced Liver Injury.

    abstract::Human hepatocellular carcinoma cells, HepG2, are often used for drug mediated mitochondrial toxicity assessments. Glucose in HepG2 culture media is replaced by galactose to reveal drug-induced mitochondrial toxicity as a marked shift of drug IC50 values for the reduction of cellular ATP. It has been postulated that ga...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/acs.chemrestox.9b00033

    authors: Xu Q,Liu L,Vu H,Kuhls M,Aslamkhan AG,Liaw A,Yu Y,Kaczor A,Ruth M,Wei C,Imredy J,Lebron J,Pearson K,Gonzalez R,Mitra K,Sistare FD

    更新日期:2019-08-19 00:00:00

  • Metabolomic characterization of laborers exposed to welding fumes.

    abstract::The complex composition of welding fumes, multiplicity of molecular targets, diverse cellular effects, and lifestyles associated with laborers vastly complicate the assessment of welding fume exposure. The urinary metabolomic profiles of 35 male welders and 16 male office workers at a Taiwanese shipyard were character...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx200465e

    authors: Wang KC,Kuo CH,Tian TF,Tsai MH,Chiung YM,Hsiech CM,Tsai SJ,Wang SY,Tsai DM,Huang CC,Tseng YJ

    更新日期:2012-03-19 00:00:00

  • DNA Product Formation in Female Sprague-Dawley Rats Following Polyhalogenated Aromatic Hydrocarbon (PHAH) Exposure.

    abstract::DNA oxidation damage has been regarded as one of the possible mechanisms for the hepatic carcinogenesis of dioxin-like compounds (DLCs). In this study, we evaluated the toxic equivalency factor (TEF) from the standpoint of induced DNA oxidation products and their relationship to toxicity and carcinogenicity. Nine DNA ...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/acs.chemrestox.6b00368

    authors: Gao L,Mutlu E,Collins LB,Walker NJ,Hartwell HJ,Olson JR,Sun W,Gold A,Ball LM,Swenberg JA

    更新日期:2017-03-20 00:00:00

  • Chalcone inhibition of anthracycline secondary alcohol metabolite formation in rabbit and human heart cytosol.

    abstract::Antineoplastic therapy with anthracyclines like doxorubicin (DOX) and daunorubicin (DNR) is limited by the possible development of a dose-related cardiomyopathy. Secondary alcohol metabolites like doxorubicinol (DOXol) and daunorubicinol (DNRol), formed by cytoplasmic two-electron reductases, have been implicated as p...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx060159a

    authors: Silvestrini A,Meucci E,Vitali A,Giardina B,Mordente A

    更新日期:2006-11-01 00:00:00

  • Synthesis and characterization of adducts derived from the syn-diastereomer of benzo[a]pyrene 7,8-dihydrodiol 9,10-epoxide and the 5'-d(CCTATAGATATCC) oligonucleotide.

    abstract::5'-d(CCTATAGATATCC) was reacted with each syn-enantiomer of trans-7,8-dihydroxy 9,10-epoxy 7,8,9,10-tetrahydrobenzo[a]pyrene (syn-BPDE). The (-)-enantiomer yielded one dominating adduct, whereas the (+)-enantiomer resulted in two major adducts. As indicated by optical spectroscopic methods, the major adduct derived fr...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx950041m

    authors: Pontén I,Seidel A,Gräslund A,Jernström B

    更新日期:1996-01-01 00:00:00

  • Oxidative activation of thiacetazone by the Mycobacterium tuberculosis flavin monooxygenase EtaA and human FMO1 and FMO3.

    abstract::Thiacetazone (TAZ) and ethionamide (ETA) are, respectively, thiourea- and thioamide-containing second line antitubercular prodrugs for which there is an extensive clinical history of cross-resistance in Mycobacterium tuberculosis. EtaA, a recently identified flavin-containing monooxygenase (FMO), is responsible for th...

    journal_title:Chemical research in toxicology

    pub_type: 杂志文章

    doi:10.1021/tx050328b

    authors: Qian L,Ortiz de Montellano PR

    更新日期:2006-03-01 00:00:00