Adrenocorticolytic derivatives of benz[.alpha.]anthracene

Pataki, J.; Wlos, R.; Cho, Young-Ja

doi:10.1021/jm00311a047

Cited by 16 publications

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“…7-Formyl-12-methyllbenz[ a ]anthracene (7-CHO-12-MBA) and 12-Formyl-7-methyllbenz[ a ]anthracene (12-CHO-7-MBA) were synthesized by oxidation of 7-HOCH 2 -12-MBA and 12- HOCH 2 -7-MBA, respectively with DDQ [25]. 7,12-Epidioxy-7,12-dihydro-DMBA was prepared according to Wood et al [26].…”

Section: Methodsmentioning

confidence: 99%

“…According to the method published by Boyland and Sims [ 24 ], 7-HOCH 2 -12-MBA and 12-HOCH 2 -7-MBA were prepared by reaction of DMBA with lead tetraacetate, separation of the resulting 7-acetoxymethyl-12-MBA and 12-acetoxymethyl-7-MBA by column chromatography, and hydrolysis to the hydroxyl DMBA. 7-Formyl-12-methyllbenz[ a ]anthracene (7-CHO-12-MBA) and 12-Formyl-7-methyllbenz[ a ]anthracene (12-CHO-7-MBA) were synthesized by oxidation of 7-HOCH 2 -12-MBA and 12- HOCH 2 -7-MBA, respectively with DDQ [ 25 ]. 7,12-Epidioxy-7,12-dihydro-DMBA was prepared according to Wood et al [ 26 ].…”

Section: Methodsmentioning

confidence: 99%

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Photochemical Reaction of 7,12-Dimethylbenz[a]anthracene (DMBA) and Formation of DNA Covalent Adducts

Yan

Jiao

et al. 2005

IJERPH

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DMBA,7,anthracene, is a widely studied polycyclic aromatic hydrocarbon that has long been recognized as a probable human carcinogen. It has been found that DMBA is phototoxic in bacteria as well as in animal or human cells and photomutagenic in Salmonella typhimurium strain TA102. This article tempts to explain the photochemistry and photomutagenicity mechanism. Light irradiation converts DMBA into several photoproducts including benz[a]anthracene-7,12-dione, 7-hydroxy-12-keto-7-methylbenz[a]anthracene, 7,12-epidioxy-7,12-dihydro-DMBA, 7-hydroxymethyl-12-methylbenz[a]anthracene and 12-hydroxymethyl-7-methylbenz[a]anthracene. Structures of these photoproducts have been identified by either comparison with authentic samples or by NMR/MS. At least four other photoproducts need to be assigned. Photo-irradiation of DMBA in the presence of calf thymus DNA was similarly conducted and light-induced DMBA-DNA adducts were analyzed by 32 P-postlabeling/TLC, which indicates that multiple DNA adducts were formed. This indicates that formation of DNA adducts might be the source of photomutagenicity of DMBA. Metabolites obtained from the metabolism of DMBA by rat liver microsomes were reacted with calf thymus DNA and the resulting DNA adducts were analyzed by 32 P-postlabeling/TLC under identical conditions. Comparison of the DNA adduct profiles indicates that the DNA adducts formed from photo-irradiation are different from the DNA adducts formed due to the reaction of DMBA metabolites with DNA. These results suggest that photo-irradiation of DMBA can lead to genotoxicity through activation pathways different from those by microsomal metabolism of DMBA.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Photochemical Reaction of 7,12-Dimethylbenz[a]anthracene (DMBA) and Formation of DNA Covalent Adducts

Yan

Jiao

et al. 2005

IJERPH

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A simple method for the synthesis of specific [²H] and [³H]labelled methyl‐hydroxylated derivatives of 7,12‐dimethylbenz[a]anthracene

Yang

1979

Labelled Comp Radiopharmac

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Specific [ ' H I and [ 3H] labelled methyl-hydroxylated derivatives of 7,12-dimethylbenz[a]anthracene (DMBA), 7-hydroxymethyl-12methylbenz[a]anthracene, 7-methyl-12-hydroxymethylbenz[a]anthracene, and 7,12-dihydroxymethylbenz[a]anthracene, were synthesized with good yield and high specific activity. method involved two simple steps; oxidation of the unlabelled methyl-hydroxylated DMBA to the corresponding forrnyl derivatives followed by reduction with either sodium borodeuteride or sodium borotriteride to yield the [ ' H I or [3H]labelled methyl-hydroxylated derivatives with the isotope specifically attached to benzylic carbons. The

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Mass spectrometric analysis of 7‐sulfoxymethyl‐12‐methylbenz[a]anthracene and related electrophilic polycyclic aromatic hydrocarbon metabolites

2004

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The Meso-region theory of polycyclic aromatic hydrocarbon (PAH) carcinogenesis predicts that the development of pronounced carcinogenicity depends on the introduction of a good leaving group on alkyl side-chains attached to the exceptionally reactive meso-anthracenic or L-region positions of PAHs. Thus, the first step in carcinogenesis by methylated PAHs such as 7,12-dimethylbenz[a]anthracene (DMBA) would be the hydroxylation of the L-region methyl groups, particularly the 7-methyl group. The second would be the formation of a metabolite, e.g. a sulfate ester, which is expected to be a good leaving group capable of generating a highly reactive benzylic carbocation. 7-Hydroxymethyl-12-methylbenz[a]anthracene (7-HMBA) is a metabolite of DMBA, and sulfation of 7-HMBA to a 7-sulfoxymethyl metabolite (7-SMBA) is a known Phase II metabolic process designed to facilitate excretion, but actually enabling more destructive side-reactions. These side-reactions occur with generation of an electrophilic 7-methylene carbonium ion, and/or by in vivo halide exchange to provide neutral side-products more capable of entering cells, especially those of DMBA target tissues. Electrospray ionization mass spectrometry (MS) enabled us to visualize 7-SMBA as an intact m/z 351 conjugate anion by negative mode, and as a released m/z 255 carbonium ion by positive mode. Upon prolonged refrigeration, 7-SMBA accumulated an m/z 383 photooxide, which appeared capable of re-evolving the starting material as visualized by tandem quadrupole MS, or MS/MS. The 7-SMBA carbonium ion provided interpretable fragments when studied by fragment ion MS/MS, including those representing the loss of up to several protons. Subtle differences in this property were encountered upon perturbing 7-SMBA, either by warming it at 37 degrees C for 2 h or by substituting the initial sulfoxy group with an iodo group. Side-reactions accounting for such proton losses are proposed, and are of interest whether they occur in the mass spectrometer, in solution or both; these proposals include acidity at the 12-methyl position and cyclization between the 12-methyl group and the adjacent C-1 position. It is also suggested that such side-reactions may comprise one route to relieving steric strain arising between the 12-methyl group and the angular benzo ring of 7-SMBA.

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Adrenocorticolytic derivatives of benz[.alpha.]anthracene

Cited by 16 publications

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Photochemical Reaction of 7,12-Dimethylbenz[a]anthracene (DMBA) and Formation of DNA Covalent Adducts

Photochemical Reaction of 7,12-Dimethylbenz[a]anthracene (DMBA) and Formation of DNA Covalent Adducts

A simple method for the synthesis of specific [²H] and [³H]labelled methyl‐hydroxylated derivatives of 7,12‐dimethylbenz[a]anthracene

Mass spectrometric analysis of 7‐sulfoxymethyl‐12‐methylbenz[a]anthracene and related electrophilic polycyclic aromatic hydrocarbon metabolites

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Adrenocorticolytic derivatives of benz[.alpha.]anthracene

Cited by 16 publications

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Photochemical Reaction of 7,12-Dimethylbenz[a]anthracene (DMBA) and Formation of DNA Covalent Adducts

Photochemical Reaction of 7,12-Dimethylbenz[a]anthracene (DMBA) and Formation of DNA Covalent Adducts

A simple method for the synthesis of specific [2H] and [3H]labelled methyl‐hydroxylated derivatives of 7,12‐dimethylbenz[a]anthracene

Mass spectrometric analysis of 7‐sulfoxymethyl‐12‐methylbenz[a]anthracene and related electrophilic polycyclic aromatic hydrocarbon metabolites

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A simple method for the synthesis of specific [²H] and [³H]labelled methyl‐hydroxylated derivatives of 7,12‐dimethylbenz[a]anthracene