- Ultraviolet-photoproduct of acetaminophen: Structure determination and evaluation of ecotoxicological effect
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This study was focused on photodegradation of acetaminophen (AA) exposed to ultraviolet (UV) irradiation at 254 nm delivered by a system similar to that used for sterilization in sewage treatment plants. The degradation of AA during irradiation for up to 96 h was monitored by means of high-performance liquid chromatography (HPLC). Based on the mass/charge ratio (m/z) of the protonated ion and the mass fragmentation pattern in electrospray ionization time-of-flight mass spectrometry (ESI-TOF/MS/MS), the photoproduct was identified as 1-(2-amino-5-hydroxyphenyl)ethanone (1). Examination of toxicity by means of a luminescent bacteria test (ISO11348) indicated that AA solution was nontoxic, whereas photo-exposed AA solution was toxic (EC50: 29.46 mg/L). The toxicity of synthetic compound 1 was shown to account for a substantial part of the toxicity of photo-exposed AA. These results indicate the importance of investigating not only parent compounds, but also photoproducts the risk assessment of pharmaceuticals in aquatic environments.
- Kawabata, Kohei,Sugihara, Kazumi,Sanoh, Seigo,Kitamura, Shigeyuki,Ohta, Shigeru
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- Wavelength-dependent photochemistry of acetaminophen in aqueous solutions
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The influence of irradiation wavelength and intensity on photochemistry of acetaminophen (APAP) in aqueous solution was investigated by combination of steady-state and laser flash photolysis as well as HPLC and LC-MS. Steady-state irradiation at 254 nm leads to APAP disappearance with the quantum yield 0.0014 and to formation of 1-(2-amino-5-hydroxyphenyl)ethanone (P1) as a main primary photo-Fries product. In opposite the laser excitation at 266 nm leads predominantly to two-photon ionization of APAP with the quantum yield 0.013 (I = 70 mJ/cm2) and to the formation of one main product of phenoxyl radical reactions - N-(3,4-dihydroxyphenyl)acetamide (P5). Steady-state excitation at 282 nm leads to both P1 and P5 products formation indicating competition of photo-Fries and photoionization processes. The wavelength-dependent mechanism of APAP photolysis is proposed and discussed.
- Pozdnyakov, Ivan P.,Zhang, Xu,Maksimova, Tatiana A.,Yanshole, Vadim V.,Wu, Feng,Grivin, Vjacheslav P.,Plyusnin, Victor F.
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p. 117 - 123
(2013/12/04)
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- Mechanistic pathways of the photolysis of paracetamol in aqueous solution: An example of photo-Fries rearrangement
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The mechanism of the photolysis of N-(4-hydroxyphenyl)ethanamide (paracetamol, PA), a widely prescribed analgesic and antipyretic drug, has been investigated in the absence and in the presence of oxygen. Identification of products and kinetic analyses were performed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) and by ultra-performance liquid chromatography with a diode array detector (UPLC-PDA). The results show that, under irradiation at 254 nm and independently of the presence of oxygen, the predominant reaction pathway is a photo-Fries rearrangement (PFR), yielding the PA isomer 2′-amino-5′-hydroxyacetophenone (PAI). This reaction occurs from the singlet excited state of the molecule and involves the migration of the acetyl group onto the aromatic ring in the ortho-position to the amine moiety. The formation of 4-aminophenol (4-AP) was observed as a minor competitive pathway. The quantum yield of PA consumption (Φ-PA) was determined to be 1.0(±0.1) × 10-3 by chemical actinometry. As its concentration increases, the PFR product (PAI) competes with PA for light absorption and undergoes, in the presence of oxygen, a photooxygenation process leading to the formation of a peroxyester.
- Martignac, Marion,Oliveros, Esther,Maurette, Marie-Therese,Claparols, Catherine,Benoit-Marquie, Florence
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p. 527 - 535
(2013/07/19)
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- Topoisomerase I-mediated antiproliferative activity of 10-substituted and 12-substituted homocamptothecins
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Homocamptothecin (hCPT) is an E-ring modified camptothecin (CPT) analogue, which showed pronounced inhibitory activity of topoisomerase I. In search of novel hCPT-type anticancer agents, two series of hCPT derivatives were synthesized and evaluated in vitro against three human tumor cell lines. The results indicated that the 10-substituted hCPT derivatives had a considerably higher cytotoxic activity than the 12-substituted ones. Among the 10-substituted compounds, 8a, 8b, 9b, and 9i showed an equivalent or even more potent activity than the positive control drug topotecan against the lung cancer cell line A-549. Moreover, the hCPT analogues 8a and 8b exhibited a higher topoisomerase I inhibitory activity than CPT at a concentration of 100 μM. Copyright
- Guo, Wei,Liu, Wenfeng,Zhu, Lingjian,Zhang, Yongqiang,Cheng, Pengfei,Dong, Guoqiang,Zhuang, Chunlin,Yao, Jianzhong,Sheng, Chunquan,Miao, Zhenyuan,Zhang, Wannian
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p. 1539 - 1549
(2011/11/05)
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- Trifluoromethyl-promoted homocamptothecins: Synthesis and biological activity
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The homocamptothecin (hCPT) represents a new class of topoisomerase inhibitor which combines enhanced plasma stability and strong antitumor activity. Fluorine imparts desirable characteristics to drugs by modulating both the pharmacokinetics and pharmacodynamic properties of a drug. Therefore, in an attempt to improve the antitumor activity of homocamptothecins, seven new 7-trifluoromethylated homocamptothecin derivatives were prepared by proline-catalyzed Friedlander annulation. The antitumor activity in vitro and in vivo on cancer cell lines, and inhibitory properties of topoisomerase I-mediated DNA cleavage of compounds 6c and 8b were evaluated. Several of these trifluoromethylated hCPT derivatives (such as 6a, 6b and 6c) possessed higher in vitro antitumor activity than topotecan (TPT). Especially, the compound 6c showed effective in vivo antitumor activity comparable to that of TPT.
- Zhu, Lingjian,Miao, Zhenyuan,Sheng, Chunquan,Guo, Wei,Yao, Jianzhong,Liu, Wenfeng,Che, Xiaoying,Wang, Wenya,Cheng, Pengfei,Zhang, Wannian
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experimental part
p. 2726 - 2732
(2010/08/07)
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- Phosphate ester derivatives of homocamptothecin: Synthesis, solution stabilities and antitumor activities
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Homocamptothecins (hCPTs) represents a new promising class of topoisomerase I inhibitors with enhanced stability and superior antitumor activity. Some phosphodiesters and phosphotriesters homocamptothecin derivatives were designed and synthesized based on our previous synthetic route. The cytotoxicity in vitro on three cancer cell lines and antitumor activity in vivo, and inhibitory properties of topoisomerase I of these derivatives were evaluated. Among them compounds 24e and 24f exhibited higher cytotoxic activity than IRT and the former exhibited the best antitumor activity in vivo and solution stability both at pH 7.4 and pH 3.0.
- Miao, Zhenyuan,Zhang, Jing,You, Liang,Wang, Juan,Sheng, Chunquan,Yao, Jiangzhong,Zhang, Wannian,Feng, Hao,Guo, Wei,Zhou, Lei,Liu, Wenfeng,Zhu, Linjian,Cheng, Pengfei,Che, Xiaoying,Wang, Wenya,Luo, Chuan,Xu, Yulan,Dong, Guoqiang
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experimental part
p. 3140 - 3146
(2010/07/06)
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- New benzo[5,6]pyrrolizino[1,2-b]quinolines as cytotoxic agents
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An assessment of structure-activity relationships associated with the new benzo[5,6]pyrrolizino[1,2-b]quinoline system displaying potent in vitro cytotoxic activity against the MCF7 cell line is described.
- Perzyna, Aurore,Klupsch, Frederique,Houssin, Raymond,Pommery, Nicole,Lemoine, Amelie,Henichart, Jean-Pierre
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p. 2363 - 2365
(2007/10/03)
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