赭曲霉毒素A | 303-47-9

• 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
• 中文名称: 赭曲霉毒素A
• 中文别名: 曲霉素A；赭曲霉素；喹唑；赭曲毒素A；棕曲霉毒素A
• 英文名称: ochratoxin A
• 英文别名: OTA；(2S)-2-[[(3R)-5-chloro-8-hydroxy-3-methyl-1-oxo-3,4-dihydroisochromene-7-carbonyl]amino]-3-phenylpropanoic acid
• CAS: 303-47-9
• 化学式: C₂₀H₁₈ClNO₆
• 分子量: 403.819
• InChiKey: RWQKHEORZBHNRI-BMIGLBTASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 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：
  113
• 氢给体数：
  3
• 氢受体数：
  6

ADMET

代谢

... 曲霉毒素A通过肠道微生物群被水解成非毒性化合物（7-羧基-5-氯-8-羟基-3,4-二氢-3R-甲基异香豆素（曲霉毒素α）和苯丙氨酸）。它以曲霉毒素A、羟基化曲霉毒素A或曲霉毒素α的形式在尿液和粪便中排出。...

... Ochratoxin A is hydrolyzed by the intestinal microflora into nontoxic compounds (7-carboxy-5-chloro-8-hydroxy-3,4-dihydro-3R-methylisocoumarin (Ochratoxin alpha) and phenylalanine). It is excreted as either ochratoxin A, hydroxylated ochratoxin A or Ochratoxin alpha in both the urine and feces. ...

来源:Hazardous Substances Data Bank (HSDB)

代谢

经过注射赭曲霉毒素A的大鼠尿液中分离并鉴定出了羟基赭曲霉毒素A。通过将赭曲霉毒素A与大鼠肝微粒体和NADPH一起孵化，形成了1种主要代谢物（90%）和2种次要代谢物，这些代谢物比赭曲霉毒素A更具极性。

Hydroxyochratoxin A was isolated & identified from urine of rats after injection with ochratoxin A. By incubating ochratoxin A with rat liver microsomes & NADPH, 1 major (90%) & 2 minor metabolites, more polar than ochratoxin A, were formed.

来源:Hazardous Substances Data Bank (HSDB)

代谢

单次口服或静脉给药（2.5毫克/千克）赭曲霉毒素A给健康的成年大鼠。赭曲霉毒素A的代谢物仅从盲肠和大肠中回收。赭曲霉毒素A通过尿液和粪便排出，既有游离药物形式，也有赭曲霉毒素alpha形式。尿液中存在未识别的代谢物。

Single oral or iv dose (2.5 mg/kg) ochratoxin A admin to healthy adult rats. Ochratoxin alpha only metabolite recovered from cecum & large intestine. Ochratoxin A excreted via urine & feces, both as free drug & ochratoxin alpha. Unidentified metabolites in urine.

来源:Hazardous Substances Data Bank (HSDB)

代谢

赭曲霉毒素A可以通过结肠微生物菌群裂解成苯丙氨酸和一个毒性较低的异香豆素衍生物（赭曲霉毒素α），同时也可以被羧肽酶A和α-胰凝乳蛋白酶裂解。

Ochratoxin A is cleaved into phenylalanine and a less toxic iso-coumarin derivative (ochratoxin alpha) by the microbial flora of the colon ... and by carboxypeptidase A and alpha-chymotrypsin ... .

来源:Hazardous Substances Data Bank (HSDB)

代谢

曲霉毒素A通过结肠的微生物群、羧肽酶A和α-胰蛋白酶裂解成苯丙氨酸和一个毒性较小的异香豆素衍生物（曲霉毒素α），这是主要的代谢途径。4-羟基曲霉毒素A是主要的肝脏代谢物，其形成似乎是通过类似于脱布里佐钦4-羟基化的多态性反应。一些细胞色素P-450酶，如CYP2C9，已知能将曲霉毒素A代谢成更具细胞毒性的化合物。(T35, A2870, A3099)

Ochratoxin A is cleaved into phenylalanine and a less toxic iso-coumarin derivative (ochratoxin alpha) by the microbial flora of the colon, and by carboxypeptidase A and alpha-chymotrypsim. This is is the major metabolic pathway. 4-Hydroxyochratoxin A is the main hepatic metabolite and its formation appears to be via a polymorphic-like debrisoquine 4-hydroxylation. Some cytochrome P-450 enzymes, such as CYP2C9, and known to metabolize ochratoxin A into more cytotoxic compounds. (T35, A2870, A3099)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

曲霉毒素A已被证明具有微弱的诱变作用，可能是通过诱导氧化DNA损伤。肾毒素曲霉毒素A（OTA）会导致肾小球滤过率（GFR）和氨基马尿酸盐（PAH）清除率降低。它是一种肾毒素，能在Madin-Darby犬肾（MDCK）细胞中阻断血浆膜阴离子电导。一些细胞色素P-450酶，如CYP2C9，已知能将曲霉毒素A代谢成更具细胞毒性的化合物，这些化合物能够形成DNA加合物。（A2869, A3099）

Ochratoxin A has been shown to be weakly mutagenic, possibly by induction of oxidative DNA damage. The nephrotoxin ochratoxin A (OTA) causes a reduction of glomerular filtration rate (GFR) and of para-aminohippuric acid (PAH) clearance. It is a nephrotoxin which blocks plasma membrane anion conductance in Madin-Darby canine kidney (MDCK) cells. Some cytochrome P-450 enzymes, such as CYP2C9, are known to metabolize ochratoxin A into more cytotoxic compounds capable of forming DNA adducts. (A2869, A3099)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌性证据

评价：在人类中，对于赭曲霉毒素A的致癌性证据不足。在实验动物中，对于赭曲霉毒素A的致癌性证据充分。总体评价：赭曲霉毒素A可能对人类具有致癌性（2B组）。

Evaluation: There is inadequate evidence in humans for the carcinogenicity of ochratoxin A. There is sufficient evidence in experimental animals for the carcinogenicity of ochratoxin A. Overall evaluation: Ochratoxin A is possibly carcinogenic to humans (Group 2B).

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

赭曲霉毒素A：合理预期为人类致癌物。

Ochratoxin A: reasonably anticipated to be a human carcinogen.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌物分类

国际癌症研究机构致癌物：赭曲霉毒素A

IARC Carcinogenic Agent:Ochratoxin A

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构（IARC）致癌物分类：2B组：可能对人类致癌

IARC Carcinogenic Classes:Group 2B: Possibly carcinogenic to humans

来源:International Agency for Research on Cancer (IARC)

吸收、分配和排泄

由于由赭曲霉毒素A引起的猪霉毒肾病与巴尔干地方性肾病（BEN）之间存在病理形态学上的相似性，因此有人建议相同的病因因素在BEN中起作用。基于在猪身上进行的几个实地和实验研究的结果，开发了一种适当的分析方法来监测人类可能接触赭曲霉毒素A的情况。该毒素的毒物动力学特性具有物种特异性，尽管在所有研究的动物物种中（鱼类除外）以及人类中，血浆中都发现了两种结合蛋白。猴子具有最长的毒素消除半衰期，为510小时，相比之下，鱼的消除半衰期仅为0.68小时。鱼的肾脏显示出特定的分布模式。在产蛋鹌鹑中，最显著的观察结果是标记的赭曲霉毒素A在蛋黄中的积累。通常，（14C）赭曲霉毒素A会迅速从鹌鹑体内排出，但在小鼠的循环血液中保留时间较长。尽管赭曲霉毒素A从体内排出取决于其与血浆成分的结合，但肠肝循环的存在可能部分解释了其在哺乳动物体内的长期保留和排出。赭曲霉毒素A的毒物动力学特征并不与BEN病因学中的霉菌毒素假设相矛盾。

Since there are pathomorphological similarities between porcine mycotoxic nephropathy caused by ochratoxin A and Balkan endemic nephropathy (BEN), it has been suggested that the same aetiological agent has a role in BEN. Based on the results from several field and experimental studies carried out on pigs, an appropriate analytical method of monitoring possible human exposure to ochratoxin A was developed. The toxicokinetic properties of the toxin were species specific, although in all the animal species studied (with the exception of fish), as well as in humans, two binding proteins were found in the plasma. The monkey had the longest elimination half-life of the toxin, 510 hr, in contrast to the fish whose elimination half-life was only 0.68 hr. The fish kidney displayed a specific pattern of distribution. In the laying quail the most prominent observation was the accumulation of labelled ochratoxin A in egg yolk. Generally, (14C)ochratoxin A was eliminated rapidly from the quail body, but had a long retention time in the circulating blood in the mouse. Although the elimination of ochratoxin A from the body depending on its binding to plasma constituents, the existence of enterohepatic circulation might have been partially responsible for its prolonged retention and elimination from the body of mammals. The toxicokinetic profile of ochratoxin A did not contradict the mycotoxic hypothesis in the aetiology of BEN.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

曲霉毒素A在整个胃肠道中被迅速吸收，并在体内以双室开放模型分布，对血清白蛋白具有特别高的亲和力。曲霉毒素A通过肠道微生物群水解成非毒性化合物（7-羧基-5-氯-8-羟基-3,4-二氢-3R-甲基异香豆素（曲霉毒素α）和苯丙氨酸）。它以曲霉毒素A、羟基化曲霉毒素A或曲霉毒素α的形式通过尿液和粪便排出。曲霉毒素A通过促进脂质过氧化水平的提高、抑制氨基酸酰化反应以及可能转化为能够结合DNA的代谢物来发挥其毒性作用。这些反过来又引起与曲霉毒素A相关的其他次级效应。看来这种化合物对人类构成了真正的潜在危害，因为它的出现广泛且具有高度致癌性。

... Ochratoxin A is rapidly absorbed throughout the entire gastrointestinal tract and distributes itself in the body as a two compartment open model and has a particular high affinity for serum albumin. Ochratoxin A is hydrolyzed by the intestinal microflora into nontoxic compounds (7-carboxy-5-chloro-8-hydroxy-3,4-dihydro-3R-methylisocoumarin (Ochratoxin alpha) and phenylalanine). It is excreted as either ochratoxin A, hydroxylated ochratoxin A or Ochratoxin alpha in both the urine and feces. Ochratoxin A appears to exert its toxic effect by promoting an increased level of lipid peroxidation by inhibition of an amino acylation reaction and possibly by conversion into metabolites that are capable of binding DNA. These in turn cause other secondary effects associated with ochratoxin A. It would appear that this compound presents a true potential hazard for humans as its occurrence is wide spread and it is highly carcinogenic.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

每天用500微克赭曲霉毒素A对大鼠进行插管，或者在大麦中每天喂食250微克。肝脏或肾脏中几乎没有积累化合物。平均每天通过尿液和粪便排出的总量仅略超过给药剂量的10%。也排出了少量水解产物的量。

Rats intubated daily with 500 ug ochratoxin A or fed 250 ug daily in barley. There was little accumulation of cmpd in liver or kidneys. Avg total amount excreted daily in urine & feces was just over 10% of administered dose. Small amount of hydrolysis product also excreted.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

给予单次腹腔注射1毫克用(14)C标记的赭曲霉毒素A的大鼠。30分钟后，在血清(90%)、肝脏(4.5%)和肾脏(4.4%)中达到最高水平。赭曲霉毒素A主要通过尿液以未改变的毒素或代谢物形式排出。在粪便中的排出较少。

Rats given single ip injection of 1 mg ochratoxin A labelled with (14)C. Reached highest levels in serum (90%), liver (4.5%), & kidney (4.4%) 30 min later. Ochratoxin A was excreted primarily in urine as unchanged toxin or metabolites. Excretion in feces less significant.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 储存条件：
  储存温度为2-8°C。

制备方法与用途

赭曲霉毒素A是一种典型的曲霉属真菌毒素，常见于谷物、咖啡、葡萄、葡萄酒和啤酒等中的次级代谢产物。

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  tert-butyl N-(((3R)-5-chloro-8-hydroxy-3-methyl-1-oxoisochroman-7-yl)carbonyl)-L-phenylalaninate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 以99%的产率得到赭曲霉毒素A
  参考文献：
  名称：

  钌-NHC-二胺催化异香豆素的对映选择性氢化

  摘要：

  公开了一种新颖实用的手性钌-NHC-二胺体系，用于异香豆素的对映选择性氢化，为将（手性）NHC配体应用于不对称催化提供了一个新概念。以优异的对映选择性（高达 99% ee）获得了多种光学活性 3-取代的 3,4-二氢异香豆素。此外，该方法还用于合成 O-甲基蜜蜡、蜜蜡和赭曲霉毒素 A。

  DOI：

  10.1021/jacs.6b13124

文献信息

• Structural and functional characterization of ochratoxinase, a novel mycotoxin-degrading enzyme
  作者：Doreen Dobritzsch、Huaming Wang、Gunter Schneider、Shukun Yu

  DOI：10.1042/bj20140382

  日期：2014.9.15

  produced by Aspergillus and Penicillium species and occurs in a wide range of agricultural products. Detoxification of contaminated food is a challenging health issue. In the present paper we report the identification, characterization and crystal structure (at 2.2 Å) of a novel microbial ochratoxinase from Aspergillus niger. A putative amidase gene encoding a 480 amino acid polypeptide was cloned

  曲霉毒素以曲霉毒素A为主要形式，是对人类和动物最有害的五种主要霉菌毒素之一。它由曲霉和青霉菌种产生，并存在于多种农产品中。对受污染食品进行排毒是一个具有挑战性的健康问题。在本文中，我们报道了一种来自黑曲霉的新型微生物曲霉毒素酶的鉴定，表征和晶体结构（在2.2Å下）。克隆了一个假定的编码480个氨基酸多肽的酰胺酶基因，并在黑曲霉中同源表达。重组蛋白是N端截短的，热稳定的，在pH〜6和66°C下具有最佳活性，并且在ra曲霉毒素A水解中比羧肽酶A和Y（这两种已知的能够降解这种霉菌毒素的酶）更有效。同八聚体酶的亚基折叠成金属依赖性酰胺水解酶的两个结构域结构特征，具有扭曲的TIM（三磷酸磷酸异构酶）桶和较小的β-夹心结构域。该活性位点包含用于酸碱催化的天冬氨酸残基，以及用于结合双核金属中心的羧化赖氨酸残基和四个组氨酸残基。
• Array Biosensor for Detection of Ochratoxin A in Cereals and Beverages
  作者：Miriam M. Ngundi、Lisa C. Shriver-Lake、Martin H. Moore、Michael E. Lassman、Frances S. Ligler、Chris R. Taitt

  DOI：10.1021/ac048957y

  日期：2005.1.1

  Contamination of food by mycotoxins occurs in minute quantities, and therefore, there is a need for a highly sensitive and selective device that can detect and quantify these organic toxins. We report the development of a rapid and highly sensitive array biosensor for the detection and quantitation of ochratoxin A (OTA). The array biosensor utilizes a competitive immunoassay format. Immobilized OTA derivatives compete with toxin in solution for binding to fluorescent anti-OTA antibody spiked into the sample. This competition is quantified by measuring the formation of the fluorescent immunocomplex on the waveguide surface. The fluorescent signal is inversely proportional to the concentration of OTA in the sample. Analyses for OTA in buffer and a variety of food and beverage samples were performed. Samples were extracted with methanol, without any sample cleanup or preconcentration step prior to analysis. The limit of detection for OTA in several cereals ranged from 3.8 to 100 ng/g, while in coffee and wine, detection limits were 7 and 38 ng/g, respectively.

  霉菌毒素对食品的污染发生在微量水平，因此需要一种高度灵敏且有选择性的装置来检测和定量这些有机毒素。我们报告了开发一种用于检测和定量赭曲霉毒素A（OTA）的快速且高度灵敏的阵列生物传感器。该阵列生物传感器利用竞争性免疫分析格式。固定化的OTA衍生物与溶液中的毒素竞争结合加入样品中的荧光抗OTA抗体。通过测量波导表面荧光免疫复合物的形成来量化这种竞争。荧光信号与样品中OTA的浓度成反比。对缓冲液及多种食品和饮料样品中的OTA进行了分析。样品用甲醇提取，分析前无需任何样品净化或预浓缩步骤。几种谷物中OTA的检测限介于3.8至100纳克/克之间，而在咖啡和葡萄酒中，检测限分别为7和38纳克/克。
• 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
• Metabolism of Ochratoxin A:  Absence of Formation of Genotoxic Derivatives by Human and Rat Enzymes
  作者：Jean-Charles Gautier、Janique Richoz、Dieter H. Welti、Jovanka Markovic、Eric Gremaud、F. Peter Guengerich、Robert J. Turesky

  DOI：10.1021/tx000070j

  日期：2001.1.1

  and OTA products were not formed with horseradish peroxidase. There was no evidence of DNA adduct formation when [(3)H]OTA was incubated with these enzyme systems in the presence of calf thymus DNA (<20 adducts/10(9) DNA bases); however, these enzymes catalyzed DNA adduct formation with the genotoxins aflatoxin B(1), 2-amino-3-methylimidazo[4,5-f]quinoline, benzo[a]pyrene, and pentachlorophenol. There

  ch曲毒素A（OTA）在雄性大鼠中是一种强效的肾脏致癌物，尽管其致癌性模式尚不清楚。用细胞色素P450，谷胱甘肽S-转移酶，前列腺素H-合酶和辣根过氧化物酶体外研究了OTA与DNA的代谢和共价结合。将OTA与用NADPH强化的大鼠或人肝微粒体一起孵育可导致低速率[10-25 pmol min（-1）（mg蛋白质）（-1）]形成4-（R）-羟基och曲霉毒素A。没有证据表明大鼠，小鼠或人肾微粒体或线粒体后上清液（S-9）的OTA代谢和谷胱甘肽共轭物形成[<5 pmol min（-1）（mg蛋白）（-1）]。重组人细胞色素P450（P450）1A1和3A4以低比率形成[4-（R）-羟基p曲霉毒素A [分别为0.08和0.06 pmol min（-1）（pmol P450）（-1）]；用重组人P450 1A2或2E1或大鼠P450 1A2或2C11未检测到OTA的氧化产物[<0.02 pmol min（-1）（pmol
• On the role of copper and iron in DNA cleavage by ochratoxin A. Structure-activity relationships in metal binding and copper-mediated DNA cleavage
  作者：Jason A Ardus、Ivan G Gillman、Richard A Manderville

  DOI：10.1139/v98-088

  日期：1998.6.1

  Ochratoxin A (OTA, 1: X = Cl) is a fungal carcinogen that facilitates single-strand DNA cleavage and DNA adduction when metabolically activated. To determine if redox-active transition metals induce OTA-mediated DNA damage, we have examined the toxin's ability to bind Cu(II) and Fe(III) in aqueous media and facilitate DNA cleavage in their presence using agarose gel electrophoresis and supercoiled plasmid DNA. Using fluorescence spectroscopy, 1 was found to bind Cu(II) readily at physiological pH, while acidic conditions (pH 2.6) were employed to study Fe(III) binding due to the formation of Fe-oxide precipitates at higher pH values. Structure-activity relationships employing synthetic derivatives of 1 implied that 1 binds both Cu(II) and Fe(III) by its phenolic oxygen, while the carboxylic acid of its phenylalanine moiety binds Cu(II), but does not appear to play a role in Fe(III) coordination at pH 2.6. In terms of metal-mediated DNA cleavage, no role for 1 could be detected in Fe-induced DNA strand scission. With Cu(II), DNA cleavage by the 1:1 copper-bound complex of 1 could only be initiated by addition of a suitable reducing agent (sodium ascorbate). However, 1 was found to facilitate DNA cleavage by the Cu(II) complex of 1,10-phenanthroline (Cu(OP)₂); a prototypical Cu-mediated nuclease system that cleaves DNA upon activation by an external reducing agent. Structure-activity relationships employing analogs lacking the chlorine atom, ochratoxin B (2: X = H), and the lactone (12), indicated that the chlorine atom is essential for activity of the OTA in potentiating DNA cleavage by Cu(OP)₂. The implications of our findings to the genotoxic properties of 1 are discussed.Key words: ochratoxin, DNA cleavage, copper, iron, 1,10-phenanthroline.

  奥克拉毒素A（OTA，1：X = Cl）是一种真菌致癌物质，当在代谢活化时，它促进单链DNA断裂和DNA加合物的形成。为了确定氧化还原活性过渡金属是否诱导OTA介导的DNA损伤，我们研究了毒素在水介质中结合Cu（II）和Fe（III）的能力，并在它们的存在下利用琼脂糖凝胶电泳和超螺旋质粒DNA促进DNA断裂。利用荧光光谱，发现1在生理pH下能够很容易地结合Cu（II），而在酸性条件（pH 2.6）下用于研究Fe（III）结合，因为在较高pH值下会形成Fe-氧化物沉淀。利用1的合成衍生物进行结构活性关系研究表明，1通过其酚氧结合Cu（II）和Fe（III），而其苯丙氨酸部分的羧酸结合Cu（II），但在pH 2.6下似乎不参与Fe（III）的配位。在金属介导的DNA断裂方面，未发现1在Fe诱导的DNA链切断中起作用。对于Cu（II），只有通过添加适当的还原剂（抗坏血酸钠）才能启动1的1：1铜结合复合物引发的DNA断裂。然而，发现1能够通过1,10-邻菲啰啉（Cu（OP）2）的Cu（II）复合物促进DNA断裂；这是一种原型的Cu介导核酸酶系统，只有在外部还原剂的激活下才能切割DNA。通过缺乏氯原子的类似物进行结构活性关系研究，如奥克拉毒素B（2：X = H）和内酯（12），表明氯原子对于OTA在促进Cu（OP）2介导的DNA断裂中的活性是必不可少的。我们的研究结果对于1的遗传毒性特性的影响进行了讨论。关键词：奥克拉毒素，DNA断裂，铜，铁，1,10-邻菲啰啉。

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