ochratoxin hydroquinone | 205034-32-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 赭曲霉毒素及相关物质
• 英文名称: ochratoxin hydroquinone
• 英文别名: N-{[(3R)-5,8-dihydroxy-3-methyl-1-oxo-3,4-dihydro-1H-isochromen-7-yl]carbonyl}-L-phenylalanine；(2S)-2-[[(3R)-5,8-dihydroxy-3-methyl-1-oxo-3,4-dihydroisochromene-7-carbonyl]amino]-3-phenylpropanoic acid
• CAS: 205034-32-8
• 化学式: C₂₀H₁₉NO₇
• 分子量: 385.373
• InChiKey: HRZQKELUAUGJHJ-YGRLFVJLSA-N

物化性质

• 沸点：
  657.6±55.0 °C(Predicted)
• 密度：
  1.428±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  133
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  L-半胱氨酸 、 ochratoxin hydroquinone 在 phosphate buffer 作用下， 以 水 为溶剂， 反应 0.5h， 以6%的产率得到
  参考文献：
  名称：

  Photochemically Catalyzed Reaction of Ochratoxin A with D- and L-cysteine¶

  摘要：

  The photolysis (> 300 nm) of ochratoxin A (OTA, N-{[(3R)-5-chloro-8-hydroxy-3-methyl-1-oxo-7-isochromanyl]carbonyl}-3-phenyl-L-alanine, 1) in the presence of excess (2 and 12 molar equiv) cysteine (CySH) has been investigated and found to yield sulfur adducts 5 and 6 that are characterized by liquid chromatography-mass spectrometry and H-1-NMR spectroscopy. The adduct 5 was ascribed to the Michael addition conjugate resulting from covalent attachment of CySH to the ochratoxin quinone (4) generated by photooxidation of OTA. This species was also formed by photolysis of a synthetic sample of the hydroquinone of OTA (ochratoxin hydroquinone, 3) in the presence of 12 equiv L-CySH. The conjugate 5 derived from photolysis of 3 with L-CySH was used for H-1-NMR analysis. The sulfur adduct 6 was the major species detected from covalent attachment of CySH to photoactivated OTA, and it resulted from direct displacement of the OTA Cl atom by CySH. The implications of the cysteinyl adducts to the in vivo toxicity of OTA are discussed, with particular emphasis given to conjugate 5, as products from the photooxidative pathway may be of relevance to the nephrotoxic properties of OTA.

  DOI：

  10.1562/0031-8655(2002)076<0649:pcrooa>2.0.co;2
• 作为产物：
  描述：

  赭曲霉毒素A 在 phosphate buffer 作用下， 以80%的产率得到ochratoxin hydroquinone
  参考文献：
  名称：

  Ochratoxin A acts as a photoactivatable DNA cleaving agent

  摘要：

  赭曲霉毒素A通过光诱导产生DNA断裂的能力被描述；在DNA存在的情况下，光反应产生非氯化的衍生物赭曲霉毒素B，而在无氧条件下则生成氢醌衍生物。

  DOI：

  10.1039/a708275d

文献信息

• Ochratoxin A Forms a Carbon-Bonded C8-Deoxyguanosine Nucleoside Adduct:  Implications for C8 Reactivity by a Phenolic Radical
  作者：Jian Dai、Marcus W. Wright、Richard A. Manderville

  DOI：10.1021/ja034221r

  日期：2003.4.1

  oxidation to yield phenoxyl radicals. The C8 position of dG is susceptible to radical attack, as was amply proven through formation of the hydroxyl radical-derived DNA lesion, 8-oxodeoxyguanosine. The adduct 4 is the first structurally characterized nucleoside adduct of a chlorophenolic toxin, and its formation has important implications for the mutagenicity of phenolic xenobiotics.

  已使用电喷雾质谱和核磁共振评估了致癌真菌毒素赭曲霉毒素 A (OTA, 1) 与脱氧鸟苷 (dG) 反应的能力。在 50 mol 当量 dG 存在下对 OTA (100 muM) 进行光激发，导致分离和鉴定 C8-脱氧鸟苷核苷加合物 4。重要的是，使用辣根过氧化物酶 (HRP)/ OTA 氧化活化后形成了相同的加合物H2O2 或过渡金属 Fe(II) 和 Cu(II)，如质谱所证实。因为人们认为 OTA 的致突变性和随后的致癌性源于氧化性 DNA 损伤（链断裂和氧化碱基产物）和鸟嘌呤特异性 DNA 加合物的形成，加合物 4 证实了 OTA 与 dG 共价反应的能力，并且对 OTA 和其他经过氧化产生苯氧基自由基的氯酚毒素的作用机制具有重要意义。dG 的 C8 位置易受自由基攻击，这一点已通过羟基自由基衍生的 DNA 损伤 8-氧代脱氧鸟苷的形成得到充分证明。加合物 4 是第一个具有结构特征
• Structure–Activity Relationships Imply Different Mechanisms of Action for Ochratoxin A-Mediated Cytotoxicity and Genotoxicity
  作者：Kheira Hadjeba-Medjdoub、Mariana Tozlovanu、Annie Pfohl-Leszkowicz、Christine Frenette、Robert J. Paugh、Richard A. Manderville

  DOI：10.1021/tx200406c

  日期：2012.1.13

  Ochratoxin A (OTA) is a fungal toxin that is classified as a possible human carcinogen based on sufficient evidence for carcinogenicity in animal studies. The toxin is known to promote oxidative DNA damage through production of reactive oxygen species (ROS). The toxin also generates covalent DNA adducts, and it has been difficult to separate the biological effects caused by DNA adduction from that of ROS generation. In the current study, we have derived structure activity relationships (SAR) for the role of the C5 substituent of OTA (C5-X = Cl) by first comparing the ability of OTA, OTBr (C5-X = Br), OTB (C5-X = H), and OTHQ (C5-X = OH) to photochemically react with GSH and 2'-deoxyguanosine (dG). OTA, OTBr, and OTHQ react covalently with GSH and dG following photoirradiation, while the nonchlorinated OTB does not react photochemically with GSH and dG. These findings correlate with their ability to generate covalent DNA adducts (direct genotoxicity) in human bronchial epithelial cells (WI26) and human kidney (HK2) cells, as evidenced by the P-32-postlabeling technique. OTB lacks direct genotoxicity, while OTA, OTBr, and OTHQ act as direct genotoxins. In contrast, their cytotoxicity in opossum kidney epithelial cells (OK) and WI26 cells did not show a correlation with photoreactivity. In OK and WI26 cells, OTA, OTBr, and OTB are cytotoxic, while the hydroquinone OTHQ failed to exhibit cytotoxicity. Overall, our data show that the C5-Cl atom of OTA is critical for direct genotoxicity but plays a lesser role in OTA-mediated cytotoxicity. These SARs suggest different mechanisms of action (MOA) for OTA genotoxicity and cytotoxicity and are consistent with recent findings showing OTA mutagenicity to stem from direct genotoxicity, while cytotoxicity is derived from oxidative DNA damage.