Inhibition of Human Cytochrome P450 2E1 by Halogenated Anilines, Phenols, and Thiophenols(Medicinal Chemistry)
スポンサーリンク
概要
- 論文の詳細を見る
A total of 44 variously halogenated derivatives of aniline, phenol, and thiophenol were subjected to analysis of their inhibitory effect on human cytochrome P450 (CYP) 2E1 to investigate the structure-activity relationships in halogenated phenyl derivatives. The activity of human CYP2E1 of the microsomes from baculovirus-transfected insect cells expressing recombinant human CYP2E1 was determined by measuring quinoline 3-hy-droxylation, which was detectable by fluorescence monitoring (Ex=355nm and Em=460nm). Diethyldithiocarbamate (DDTC), a specific inhibitor of CYP2E1, potently inhibited quinoline 3-hydroxylation (IC_<50>=8.9μM). The effects of halogen-substitution in 32 aniline derivatives on the CYP2E1 inhibition can be summarized as follows: more enhancement by chlorine- and bromine-substitution than by fluorine-substitution, more enhancement by para- and metha-halogen-substitution than by ortho-halogen-substitution, and more enhancement by dihalogen-substitution than by mono- and trihalogen-substitution except for trifluorine-substitution. The greatest enhancement of the inhibitory activity was observed in 3,4-dichloroaniline (IC_<50>=8.0μM) and 3,5-dichloroaniline (IC_<50>=9.2μM), and their inhibitory activities were very close to that of DDTC. All of the dichlorophenols and dichlorothiophenols were compared with dichloroanilines for CYP2E1 inhibition. Although dichlorothiophenols showed similar or more potent inhibitory activities than dichloroanilines, dichlorophenols showed less inhibitory activities. 3,4-Dichlorothiophenol and 3,5-dichlorothiophenol showed very potent inhibition and their IC_<50> values were 5.3 and 5.2μM, respectively. These results suggest that 3,4- and 3,5-dichlorophenyl derivatives may be useful as potent CYP2E1 inhibitors.
- 公益社団法人日本薬学会の論文
- 2005-07-01
著者
-
松田 知成
京都大学大学院地球環境学堂環境調和型産業論分野
-
Saeki Ken-ichi
エーザイ
-
Saeki K
Graduate School Of Pharmaceutical Sciences Nagoya City University
-
Saeki Ken-ichi
名古屋市立大学 薬
-
Saeki Kenichi
Graduate School Of Pharmaceutical Sciences Nagoya City University
-
Saeki Ken-ichi
Faculty Of Pharmaceutical Sciences Nagoya City University
-
Saeki Ken-ichi
エーザイ薬理安全性研究所
-
Mizutani Takaharu
Graduate School of Pharmaceutical Sciences, Nagoya City University
-
Ohashi Yohei
Graduate School of Pharmaceutical Sciences, Nagoya City University
-
Yamada Katsuya
Graduate School of Pharmaceutical Sciences, Nagoya City University
-
TAKEMOTO Ikuyo
Graduate School of Pharmaceutical Sciences, Nagoya City University
-
Yamada K
Graduate School Of Pharmaceutical Sciences Kyushu University
-
Ohashi Yohei
Graduate School Of Pharmaceutical Sciences Nagoya City University
-
Takemoto Ikuyo
Graduate School Of Pharmaceutical Sciences Nagoya City University
-
Yamada Katsuya
Graduate School Of Pharmaceutical Sciences Nagoya City University
-
Mizutani Takaharu
Graduate School Of Pharmaceutical Sciences Nagoya City Univ.
-
Mizutani Takaharu
Graduate School Of Pharmaceutical Sciences Nagoya City University
-
Yamada Kenji
Tokyo University Of Pharmacy And Life Sciences School Of Pharmacy
関連論文
- P-025(O-2) ライフステージ(週齢)を考慮したアクリルアミドの多臓器遺伝毒性評価(ポスターセッション)
- 琵琶湖疏水におけるラン藻類とその含有毒素ミクロシスチンの挙動
- Modification of the Carcinogenic Potency of Quinoline, a Hepatocarcinogen, by Fluorine Atom Substitution : Evaluation of Carcinogenicity by a Medium-Term Assay
- Clastogenicity of Quinoline Derivatives in the Liver Micronucleus Assay Using Rats and Mice
- Clastogenicity of Quinoline and Monofluorinated Quinolines in Chinese Hamster Lung Cells
- P-063 大気汚染物質3-ニトロベンズアントロンによるDNA付加体の生成および修復の効率(ポスターセッション)
- P029 LC/MS/MSを用いたニトロ多環芳香族炭化水素によるDNA付加体および酸化損傷の分析(ポスターセッション)
- MS-3 1-ニトロピレン並びに3-ニトロベンズアントロンのDNAアダクトーム及び突然変異解析(ミニシンポジウム : 質量分析器を用いたDNA損傷の高感度解析)
- P-73 ヒト尿中のN^2-ethyl-deoxyguanosineの定量分析
- タンデム質量分析計を用いたDNA付加体のモニタリング法の開発 (京都大学環境衛生工学研究会 第19回シンポジウム講演論文集(1997年7月24日・25日,京都)) -- (一般講演)
- P-31 2'-deoxyxanthosineおよび8-nitro-2'-deoxyguanosineの誤塩基対形成機構(ポスター(1))
- P31 ホルムアルデヒドによって生成するDNA付加体の定量法の開発
- P-011(O1-10) N^2-Methyl-dGの変異スペクトル解析
- P-1 N^2-methyl-dGの変異スペクトルの解析
- 英虞湾におけるエストロゲン様物質の挙動
- 1K16-5 HPLC-バイオアッセイ検出法による水質試料のエストロゲン様物質の分析
- 140 水環境における17βエストラジオールの生分解
- 琵琶湖におけるアオコ毒素ミクロシスチンの動態と ELISA 法を用いた毒素分析に関する検討
- ラン藻類の増殖とその含有毒素の挙動
- EN-1 LC/MS/MSを用いたDNA付加体の網羅的解析に関する研究(平成21年度日本環境変異原学会 研究奨励賞,受賞講演(学会賞・功労賞・研究奨励賞))
- 液体クロマトグラフィータンデム質量分析法を用いたDNA損傷研究法
- P-023 安定同位体標識アミノ酸とタグを用いた二重標識法(DLIAA法)によるシステインのチオール基の酸化的修飾の定量的プロテオーム解析(ポスターセッション)
- P134 石油化学廃水処理場におけるDNA損傷性物質とAhRリガンドの動態についての研究
- 4-5 特別講義・セミナー(事業活動)
- 屎尿分離トイレを用いた尿からのMAP回収プラントの開発
- AhRの内因性リガンド : 外因性リガンド多環芳香族類と内因性リガンド-インディゴ・インディルビン
- P-35 新規脂質過酸化生成物4-oxo-2-hexenalの変異原性、DNA付加体形成ならびに食品中含量(ポスター(1))
- S2-1 DNA付加体高感度定量法とその応用(シンポジウム(2)「細胞がん化のブラックボックスに挑む」)
- 尿中リン回収のためのMAP生成反応の平衡モデルによる予測
- 研究室紹介 松井研究室紹介--京都大学地球環境学堂地球親和技術学廊環境調和型産業論分野
- DNA付加体の分析方法 : LC/ESI/MS/MSはポストラベルを越えたか?
- P1-016 多環芳香族化合物類(PACs)による代謝酵素誘導とDNA付加体生成(DNA損傷)
- Activation of the Human Ah Receptor by Aza-Polycyclic Aromatic Hydrocarbons and Their Halogenated Derivatives
- 多環芳香族キノン、ケトン類の芳香族炭化水素レセプター(AhR)リガンド活性
- 研究課題 GISを利用した環境微量汚染毒性物質の流域内分布と挙動解析に関する研究 : 野洲川流域を対象にして(2.2一般研究)([2]共同利用研究)
- Activation of the Aryl Hydrocarbon Receptor by Methyl Yellow and Related Congeners : Structure-Activity Relationships in Halogenated Derivatives
- 家庭排水中の内分泌攪乱化学物質(環境ホルモン) (特集 環境ホルモンと水処理)
- 天然および人工エストロゲンの下水道と環境中での挙動 (内分泌かく乱物質研究の最前線) -- (内分泌活性物質の生体および環境中での挙動)
- P-2 N^2-methyl-dGTPの大腸菌DNAポリメラーゼによるDNAへの挿入
- Nucleophilic Substitution Reaction in Indole Chemistry: 1-Methoxy-6-nitroindole-3-carbaldehyde as a Versatile Building Block for 2,3,6-Trisubstituted Indoles
- Synthesis of Nb-acyltryptamines and their 1-hydroxy-tryptamine derivatives as new α2-blockers
- Diastereoselective Synthesis of (2R, 4R)-2-Aryl-4-hydroxypyrrolidine : Preparation of the Side Chain of Novel Carbapenem
- Fluorinated Benzo[h]quinolines and Benzo[f]quinolines
- Synthesis of a Key Intermediate of Novel Galbonolide Analogues via Efficient Construction of a Conjugated Diene System
- Synthesis and Antifungal Activity of Novel 14-Membered Benzomacrolides, as Galbonolide Analogues
- Synthesis of the Side Chain of a Novel Carbapenem via Iodine-Mediated Oxidative Cyclization of (1R)-N-(1-Aryl-3-butenyl)acetamide
- Practical Synthesis of a 1β-Methylcarbapenem, J-111, 225, Using 4-Mercapto-2-[4-(N-methylaminomethyl)phenyl]pyrrolidine as a Precursor
- A Novel 1β-Methylcarbapenem, J-111,225 : Effects of the C-3 and C-5 Stereochemistry of the Pyrrolidinylthio Side Chain on Antibacterial Activities
- Clastogenicity of Quinoline Derivatives Tested by Micronucleus Induction in Vivo in the Hepatocytes of Partially Hepatectomized Mice
- P-061 多層カーボンナノチューブを曝露したマウス肺におけるDNA付加体の解析(ポスターセッション)
- Characterization of Fe(III)-Deferoxamine and Mn(II)-Pectin as Magnetic Resonance Imaging Contrast Agents
- Soluble Liver Antigen/Liver and Pancreas, an Antigen in Autoimmune Hepatitis Patients : Influence on Selenocysteine Synthesis and its Complex with HSP70
- Reactions of 1-Methoxy-3-(2-nitrovinyl)indole with Nucleophiles: An Interesting Solvent Effect and a Novel Preparation of 3-Substituted 1-Methoxyindoles
- The Chemistry of Indoles.CVII.A Novel Synthesis of3, 4, 5, 6-Tetrahydro-7-hydroxy-1H-azepino[5, 4, 3-cd]indoles and a New Finding on Pictet-Spengler Reaction
- The Chemistry of Indoles.CIII.^ Simple Syntheses of Serotonin, N-Methylserotonin, Bufotenine, 5-Methoxy-N-methyltryptamine, Bufobutanoic Acid, N-(Indol-3-yl)methyl-5-methoxy-N-methyltryptamine, and Lespedamine Based on 1-Hydroxyindole Chemistry
- Cytochrome P450 2E1/2A6-Selective Inhibition by Halogenated Anilines on Metabolic Activation of Dimethylnitrosamine in Human Liver Microsomes
- Inhibition of Human Cytochrome P450 2E1 by Halogenated Anilines, Phenols, and Thiophenols(Medicinal Chemistry)
- Phenotype Analysis of Human Cytochrome P450 2C9 Polymorphism Using a Panel of Fluorine-Substituted Benzo[h]quinolines as Inhibitors of Tolbutamide Hydroxylation
- The Influence of Quinolines on Coumarin 7- Hydroxylation in Bovine Liver Microsomes and Human CYP2A6
- Antimutagenic structural modification of quinoline assessed by an in vivo mutagenicity assay.
- Effect of 2,5-Dimethylpyrazine on Uterine Contraction in Late Stage of Pregnant Female Rats(Pharmacology)
- Isolation and Structure of a Galactocerebroside from the Sea Cucumber Bohadschia argus
- Isolation and Structure of a Monomethylated Ganglioside Possessing Neuritogenic Activity from the Ovary of the Sea Urchin Diadema setosum
- Biologically active gangliosides from echinoderms
- Determination of the Absolute Configuration of Sialic Acids in Gangliosides from the Sea Cucumber Cucumaria echinata
- Neuritogenic Activity of Gangliosides from Echinoderms and Their Structure : Activity Relationship
- Constituents of Holothuroidea, 18. Isolation and Structure of Biologically Active Disialo- and Trisialo-Gangliosides from the Sea Cucumber Cucumaria echinata
- Constituents of Holothuroidea, 17. Isolation and Structure of Biologically Active Monosialo-Gangliosides from the Sea Cucumber Cucumaria echinata
- Solvent effect on the reaction of 1-methoxy-3-(2-nitrovinyl)indole with nucleophiles
- Constituents of Holothuroidea, 16. : Determination of Absolute Configuration of the Branched Methyl Group in Ante-iso Type Side Chain Moiety on Long Chain Base of Glucocerebroside from the Sea Cucumber Holothuria leucospilota
- Constituents of Holothuroidea, 15 : Isolation of Ante-iso Type Regioisomer on Long Chain Base Moiety of Glucocerebroside from the Sea Cucumber Holothuria leucospilota
- Constituents of Holothuroidea, 14. Isolation and Structure of New Glucocerebroside Molecular Species from the Sea Cucumber Stichopus japonicus
- Novel syntheses of 1-hydroxy-6- and -5-nitroindole-3-carbaldehydes, and their derivatives as daikon-phytoalexin analogs
- Constituents of Holothuroidea, 13. Structure of Neuritogenic Active Ganglioside Molecular Species from the Sea Cucumber Stichopus chloronotus
- Nucleophilic substitution reactions of 1-methoxy-6-nitroindole-3-carbaldehyde 1
- Constituents of Holothuroidea, 12. Isolation and Structure of Glucocerebrosides from the Sea Cucumber Holothuria pervicax
- Synthesis of analogs of wasabi phytoalexin (methyl 1-methoxyindole-3-carboxylate)
- Inhibitory Effect of 2,5-Dimethylpyrazine on Oxytocic Agent -induced Uterine Hypercontraction of Normal or Pregnant Female Rats
- Synthesis of J-111,347,a Novel 1β-Methylcarbapenem with Broad-spectrum Antibacterial Activity
- P-002 / O-01 CHL/IU細胞を用いたin vitro小核試験におけるDNAアダクトーム解析(ポスターセッション)
- Effects of Benzyl Glucoside and Chlorogenic Acid from Prunus mume on Adrenocorticotropic Hormone (ACTH) and Catecholamine Levels in Plasma of Experimental Menopausal Model Rats(Pharmacognosy)
- 下水処理水中の微量化学物質と水質保全
- 天然のダイオキシン受容体リガンド,インディルビンの生理活性と製薬への応用(セミナー,生活環境と生体応答)
- P-003 CHL/IU細胞を用いたin vitro小核試験におけるDNAアダクトーム解析(第2報)(ポスターセッション)
- S2-1 質量分析器、次世代DNAシーケンサーの変異原研究への応用可能性(シンポジウム2:変異原研究の新技術、新材料)
- The Effect of Dietary Fatty Acids on the Expression Levels and Activities of Hepatic Drug Metabolizing Enzymes
- P-98 酵母株cym3を用いた環境中ダイオキシン濃度測定の試み
- O-13 重金属類によるエストロゲン受容体およびダイオキシン受容体の活性化
- バイオアッセイによる環境リスク削減評価法
- P-162 下水処理過程における女性ホルモン様活性および17βエストラジオールの挙動
- P-146(O-16) 下水のもたらすDNA損傷性と生成するDNA付加物量の関連性
- Detection of Estrogen-Like Activity in Sewage Treatment Process Waters (京都大学環境衛生工学研究会第20回シンポジウム講演論文集(1998年7月23日・24日,京都)--一般講演)
- 環境ホルモン研究の動向と展望
- 下水処理施設における女性ホルモン様物質の挙動
- 内分泌攪乱化学物質(環境ホルモン)
- DNA付加体を指標としたモニタリング法の開発
- アルデヒド類が誘発する突然変異の解析
- 水道水中有機塩素化合物のヒト細胞に対するDNA損傷性の評価
- P-008 ラットを用いた骨髄小核試験におけるDNAアダクトーム解析(ポスターセッション,安全・安心のための知的ネットワークの構築:分子生物学的からレギュラトリーサイエンスまで)
- 乳酸菌Lactobacillus fermentum 403菌が生成するオーキシン・サイトカイニンの分析方法の開発 : プロバイオティク環境農業への応用原理