The in vitro and in vivo metabolism of ... 4-nitropyrene, was studied ... Initially, 4-nitropyrene was metabolized by rat liver microsomes, or rat liver 9000g supernatant, to yield primarily two metabolites; one of these was identified as 4-nitropyrene-9,10-dione. The major metabolite of 4-nitropyrene in the presence of 3,3,3-trichloropropylene-1,2-oxide was 9,10-epoxy-9,10-dihydro-4-nitropyrene. In parallel studies, oral administration of 58 mg (0.3 mCi/mmol)/kg body weight of [3H]4-nitropyrene to female Sprague-Dawley rats, which are susceptible to mammary carcinogenesis by this agent, yielded 32% and 30.6% of the dose after 48 hr as urinary and fecal excretion products, respectively. Excretion of the radioactivity remained slightly higher in the urine than in feces throughout 168 hr after administration. Some of the fecal metabolites (isolated amounts expressed as % of dose) were identified as 4-aminopyrene (5.4), 9(10)-hydroxy-4-(acetylamino)pyrene (3.3), and unmetabolized 4-nitropyrene (2.4). Sulfates (3.3) and glucuronides (2.4) of 9(10)-hydroxy-4-(acetylamino)pyrene were identified in the urine. This study indicates that nitroreduction and ring oxidation are metabolic pathways of 4-nitropyrene in vivo; similar findings were obtained previously with its structural isomers 1- and 2-nitropyrene. However, the pattern of excretion of 4-nitropyrene is different ...
... The ability of 15 human hepatic and 8 pulmonary microsomal samples to metabolize / 1-, 2-, and 4-nitropyrene were compared/. Human hepatic microsomes were competent in metabolizing all three isomers. Qualitatively similar metabolic patterns were observed, although at much lower levels, upon incubating mono-NP with pulmonary microsomes. Ring-oxidized metabolites (phenols and trans-dihydrodiols) were produced from all three isomers. However, the nitroreductive metabolism leading to the formation of aminopyrene was evident only with 4-NP. The role of specific P450 enzymes in the human hepatic microsomal metabolism of mono-NP was investigated by correlating the P450-dependent catalytic activities in each microsomal sample with the levels of individual metabolites formed by the same microsomes and by examining the effects of agents that can either inhibit or stimulate specific P450 enzymes in mono-NP metabolism ... Most of the hepatic microsomal metabolism of 1- and 4-NP /was attributed/ to P450 3A4, although a minor role for P450 1A2 cannot be ruled out. Specifically, P450 3A4 was responsible for the formation of 3-hydroxy-1nitropyrene from 1-NP and the formation of trans-9,10-dihydro-9,10dihydroxy-4-nitropyrene, 9(10)-hydroxy-4-nitropyrene, and 4-aminopyrene from 4-NP. None of the P450 enzymes examined (P450s 3A4, 1A2, 2E1, 2A6, 2D6, and 2C9) appeared to be involved in catalyzing the formation of trans-4,5-dihydro-4,5-dihydroxy-2-nitropyrene and 6-hydroxy-2-nitropyrene from 2-NP in human hepatic microsomes ...
There is sufficient evidence for the carcinogenicity in experimental animals of 4-nitropyrene. No data were available from studies in humans on the carcinogenicity of 4-nitropyrene. 4-Nitropyrene is possibly carcinogenic to humans (Group 2B).
4-Nitropyrene is reasonably anticipated to be a human carcinogen based on sufficient evidence of malignant tumor formation at multiple tissue sites in multiple species of experimental animals.
4-Nitropyrene seems to differ from 1- and 2-nitropyrene concerning elimination and excretion patterns, metabolites and DNA adducts ... This may account for 4-nitropyrene being the most carcinogenic of the nitropyrenes in rat mammary gland.
Design, synthesis and biological evaluation of novel pyrenyl derivatives as anticancer agents
摘要：
Polycyclic aromatic hydrocarbons are widespread in nature with a toxicity range from non-toxic to extremely toxic. A series of pyrenyl derivatives has been synthesized following a four-step strategy where the pyrene nucleus is attached with a basic heterocyclic moiety through a carbon linker. Virtual screening of the physicochemical properties and druggability has been carried out. The cytotoxicity of the compounds (1-8) have been evaluated in vitro against a small panel of human cancer cell lines which includes two liver cancer (HepG2 and Hepa 1-6), two colon cancer (HT-29 and Caco-2) and one each for cervical (HeLa) and breast (MCF-7) cancer cell lines. The IC50 data indicate that compound 6 and 8 are the most effective cytotoxic agents in the present set of pyrenyl derivatives, suggesting that having a 4-carbon linker is more effective than a 5-carbon linker and the presence of amide carbonyl groups in the linker severely reduces the efficacy of the compound. The compounds showed selectivity toward cancer cells at lower doses (<5 mu M) when compared with the normal hepatocytes. The mechanism of action supports the cell death through apoptosis in a caspase-independent manner without cleavage of poly (ADP-ribose) polymerase (PARP), even though the compounds cause plasma membrane morphological changes. The compounds, whether highly cytotoxic or mildly cytotoxic, localize to the membrane of cells. The compounds with either a piperidine ring (6) or an N-methyl piperazine (8) in the side chain were both capable of circumventing the drug resistance in SKOV3-MDR1-M6/6 ovarian cancer cells overexpressing P-glycoprotein. Qualitative structure-activity relationship has also been studied. (C) 2014 Published by Elsevier Masson SAS.
Encapsulation of Pd(II) into superparamagnetic nanoparticles grafted with EDTA and their catalytic activity towards reduction of nitroarenes and Suzuki-Miyaura coupling
Fe3O4@EDTA–Pd(II) was screened for the Suzuki reaction and reduction of nitrocompounds in water. The Pd content of the catalyst was measured to be 0.28 mmol Pd g−1. In addition, the Fe3O4@EDTA–Pd catalyst can be easily separated and recovered with an external permanent magnet. The anchored solid catalyst can be recycled efficiently and reused five times with only a very slight loss of catalytic activity
Synthesis and characterisation of nitro-, nitroso- and aminofluoranthenes
作者：C. J. van Haeringen、N. F. Aten、J. Cornelisse、J. Lugtenbarg
DOI：10.1002/recl.19921110701
日期：——
The synthesis is reported of the five mononitrofluoranthenes. 1-Nitrofluoranthene was synthesized in 20% from fluoranthene, 2-nitrofluoranthene in 24% from 1,2,3,10b-tetrahydrofluoranthene, 3-nitrofluoranthene in 13% from fluoranthene and 7- and 8-nitrofluoranthene in 34% from 1,2,3,10b-tetrahydrofluoranthene. The pure nitrofluoranthenes were converted into their nitroso and amino analogues. The nitrosopyrenes
Spectroscopic and photochemical properties of mononitropyrenes
作者：A. M. van den Braken-van Leersum、C. Tintel、M. van 't Zelfde、J. Cornelisse、J. Lugtenburg
DOI：10.1002/recl.19871060403
日期：——
The influence of the nitro group on the aromatic π-system of pyrene has been studied by comparing the spectroscopic and photochemicalproperties of the three mononitropyrenes. Whereas the UV and mass spectra of 1- and 4-nitropyrene show an interaction normal for nitro-aromatic compounds, this is not observed for 2-nitropyrene. The lack of interaction is reflected in a UV spectrum very similar to that
Porphyrins with exocyclic rings. Part 24. Synthesis and spectroscopic properties of pyrenoporphyrins, potential building blocks for porphyrin molecular wires
作者：Virajkumar Gandhi、Michelle L. Thompson、Timothy D. Lash
DOI：10.1016/j.tet.2010.01.046
日期：2010.3
Porphyrins with fused pyrene units have been prepared by ‘2+2’ and ‘3+1’ methodologies. Nitration of 1,2,3,6,7,8-tetrahydropyrene, followed by oxidation with DDQ, gave 4-nitropyrene and this condensed with ethyl isocyanoacetate in the presence of DBU or a phosphazene base to generate a pyrenopyrrole ethyl ester. Ester saponification and decarboxylation with KOH in ethylene glycol at 190 °C gave the
Indium/Ammonium Chloride Mediated Selective Reduction of Aromatic Nitro Compounds: Practical Synthesis of 6-AminoChrysene
作者：Bimal K. Banik、Michelle Suhendra、Indrani Banik、Frederick F. Becker
DOI：10.1080/00397910008087002
日期：2000.10
Abstract Reduction of aromatic and heteroaromatic nitro compounds to the corresponding amino compounds was achieved by indium/ammonium chloride induced reaction in aqueous ethanol. This method was extended for the preparation of large quantities of 6-aminochrysene in excellent yield.
