57303-99-8Relevant academic research and scientific papers
Biomimetic oxidation of benzo[a]pyrene to a quinone metabolite as a cysteine-oxidation mediator on MWCNT-modified electrode surface
Nisha, Sivakumar,Senthil Kumar, Annamalai
, (2020)
Bay-region containing polyaromatic hydrocarbons (PAHs) like Benzo(a)pyrene (BaP), which comprise several strained benzenoid rings, are representative organic compounds for the carcinogenic and mutagenic activities in physiological system. In general, cytochrome c, peroxidase and certain soil-bacteria oxidize these compounds to respective hydroxylated metabolites like BaP-7,8-diol (BaP–2OH), that can interact with DNA, RNA and protein, and in turn makes the cellular system dysfunctional. The structure - activity relationship of these compounds is still unclear and therefore, it is necessary for a new analytical approach to delineate the intricate mechanism behind the oxidation of the PAHs. Herein, we report, a simple electrochemical approach of surface-confined oxidation of BaP on multiwalled carbon nanotube (MWCNT) modified glassy carbon electrode (GCE/MWCNT) in physiological condition (pH 7 phosphate buffer solution). It has been found that MWCNT-surface adsorbed BaP (electro-inactive compound) gets electro-oxidized to highly redox active BaP–2OH compound at high positive potential, 1.2 V vs Ag/AgCl, in which, the water molecule was oxidized to molecular oxygen via hydroxyl radical intermediate. From the collective electrochemical and physicochemical studies using Raman, FTIR, GC-MS and 1,2-dihydroxy redox active probe, cysteine (CySH), it has been observed that the hydroxyl radical species produced on the surface has assisted the BaP oxidation to BaP-7,8-diol product, which is similar to the biocatalyzed oxidation of BaP observed in the physiological system. The BaP-7,8-diol surface confined MWCNT modified GCE showed a well-defined and stable redox peak at an apparent standard electrode potential, Eo’ = 0 V vs Ag/AgCl. The redox process is found to be proton-coupled electron-transfer in nature. As an independent study, selective electrocatalytic oxidation of CySH has been demonstrated as an application.
Synthesis of 13C4-labelled oxidized metabolites of the carcinogenic polycyclic aromatic hydrocarbon benzo[a]pyrene
Wu, Anhui,Xu, Daiwang,Lu, Ding,Penning, Trevor M.,Blair, Ian A.,Harvey, Ronald G.
, p. 7217 - 7233 (2012/09/05)
Polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (BaP), are ubiquitous environmental contaminants that are implicated in causing lung cancer. BaP is a component of tobacco smoke that is transformed enzymatically to active forms that interact with DNA. We reported previously development of a sensitive stable isotope dilution LC/MS method for analysis of BaP metabolites. We now report efficient syntheses of 13C4-BaP and the complete set of its 13C4-labelled oxidized metabolites needed as internal standards They include the metabolites not involved in carcinogenesis (Group A) and the metabolites implicated in initiation of cancer (Group B). The synthetic approach is novel, entailing use of Pd-catalyzed Suzuki, Sonogashira, and Hartwig cross-coupling reactions combined with PtCl2-catalyzed cyclization of acetylenic compounds. This synthetic method requires fewer steps, employs milder conditions, and product isolation is simpler than conventional methods of PAH synthesis. The syntheses of 13C4-BaP and 13C4-BaP-8-ol each require only four steps, and the 13C-atoms are all introduced in a single step. 13C4-BaP-8-ol serves as the synthetic precursor of all the oxidized metabolites of 13C-BaP implicated in initiation of cancer. The isotopic purities of the synthetic 13C 4-BaP metabolites were estimated to be ≥99.9%.
Synthesis of the o-Quinones and Other Oxidized Metabolites of Polycyclic Aromatic Hydrocarbons Implicated in Carcinogenesis
Harvey, Ronald G.,Dai, Qing,Ran, Chongzhao,Penning, Trevor M.
, p. 2024 - 2032 (2007/10/03)
Efficient new syntheses of the o-quinone derivatives of benzo[a]pyrene (BPQ), 7,12-dimethylbenz-[a] anthracene (DMBAQ), and benz[a]anthracene (BAQ), implicated as active carcinogenic metabolites of the parent polycyclic aromatic hydrocarbons (PAHs), are reported. These PAH quinones also serve as starting compounds for the synthesis of the other active metabolites of these PAHs thought to be involved in their mechanism(s) of carcinogenesis. The latter include the corresponding o-catechols, trans-dihydrodiols, and the corresponding anti- and syn-diol epoxides.
Modulation of cytochrome P4501-mediated bioactivation of benzo[a]pyrene by volatile allyl sulfides in human hepatoma cells.
Chun,Kim,Choi
, p. 2205 - 2212 (2007/10/03)
Allyl sulfides such as diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), typical flavor components of Allium vegetables, have been shown to inhibit benzo[a]pyrene (B[a]P)-induced carcinogenesis in animal models. As a possible mechanism of this inhibition, the effect of these volatile substances on cytochrome P450 (CYP)1 (CYP1A1, 1A2 and 1B1)-mediated bioactivation of B[a]P was investigated using a human hepatoma cell model (HepG2). DADS and DATS inhibited the B[a]P-induced ethoxyresorufin O-deethylase (EROD) activity, a marker enzyme for CYP1, by 30-90% and 70-95% at 100-1,000 microM concentration, respectively. The cell viability, an indicator of the capacity to inhibit B[a]P bioactivation, was increased by treatments of 100-1,000 microM DADS and 10-100 microM DATS. Immunoblot results indicated that the B[a]P inducible CYP1A2 protein was suppressed by 100-1,000 microM of DADS and 10-100 microM of DATS, but CYP1A1 and 1B1 were not detectable in any microsomes. Analysis of B[a]P metabolites revealed that the level of 7,8-diol formed was significantly reduced in the DADS and DATS treated microsomes as compared to the control. The level of 9,10-diol and 4,5-diol formed was also lowered by the allyl sulfide treatments. These results suggest that the protective mechanism of allyl sulfides on B[a]P-induced carcinogenesis is possibly related with the modulation of CYP1-mediated bioactivation of B[a]P.
