sterigmatocystin | 10048-13-2

• 物质功能分类: 原料药 - 抗生素类药物 - 其它抗生素类药
• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 杂色曲霉素
• 英文名称: sterigmatocystin
• 英文别名: 3a,12c-Dihydro-8-hydroxy-6-methoxy-7H-furo(3',2':4,5)furo(2,3-c)xanthen-7-one；15-hydroxy-11-methoxy-6,8,20-trioxapentacyclo[10.8.0.02,9.03,7.014,19]icosa-1,4,9,11,14,16,18-heptaen-13-one
• CAS: 10048-13-2
• 化学式: C₁₈H₁₂O₆
• 分子量: 324.29
• InChiKey: UTSVPXMQSFGQTM-UHFFFAOYSA-N

物化性质

• 熔点：
  249-251℃
• 沸点：
  382.63°C (rough estimate)
• 密度：
  1.2842 (rough estimate)
• 闪点：
  6℃
• 溶解度：
  丙酮：5mg/mL
• LogP：
  3.169 (est)
• 物理描述：
  Solid
• 颜色/状态：
  Pale-yellow crystals
• 蒸汽压力：
  1.73X10-10 mm Hg at 25 °C (est)
• 旋光度：
  SPECIFIC OPTICAL ROTATION: -398 DEG @ 20 °C/D (CHLOROFORM, 1%)
• 保留指数：
  2999
• 稳定性/保质期：
  遵照规定使用和储存，则不会分解。

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  74.2
• 氢给体数：
  1
• 氢受体数：
  6

ADMET

代谢

在长尾猴中，主要的尿液代谢物被识别为杂色曲霉素-β-D-葡萄糖苷酸，它占到了口服剂量的75%。

In Vervet monkeys the major urinary metabolite was identified as sterigmatocystin-beta-d-glucuronide, which accounted for 75% of the oral dose administered.

来源:Hazardous Substances Data Bank (HSDB)

代谢

鹅膏蕈氨酸通过使用苯巴比妥诱导的大鼠肝微粒体进行孵化，与牛胸腺DNA共价结合。加成物被鉴定为1,2-二氢-2-(N7-鸟嘌呤基)-1-羟基鹅膏蕈氨酸。这种加成物的结构和立体化学表明，外-鹅膏蕈氨酸-1,2-氧化物是与DNA反应的代谢物，加成物的定量产率表明这种代谢物是鹅膏蕈氨酸体外代谢的主要产物。

Sterigmatocystin was covalently bound to calf thymus DNA by incubation with phenobarbital-induced rat liver microsomes. The adduct was identified as 1,2-dihydro-2-(N7-guanyl)-1-hydroxysterigmatocystin. The structure and stereochemistry of this adduct indicated that the exo-sterigmatocystin-1,2-oxide was the metabolite that reacted with DNA, and the quantitative yield of adduct indicated that this metabolite was a major product of the in vitro metabolism of sterigmatocystin.

来源:Hazardous Substances Data Bank (HSDB)

代谢

物种对杂色曲霉素毒性的敏感性顺序为：猴子大于大鼠大于小鼠。推测这些差异是由于不同物种在肝脏中杂色曲霉素分布、杂色曲霉素2,3-环氧化物形成以及肝脏微粒体中的药物代谢酶的差异造成的。

The species sensitivity to sterigmatocystin toxicity was in the order: monkey greater than rat greater than mouse. It was postulated that these differences were due to species differences in liver sterigmatocystin distribution, sterigmatocystin 2,3-epoxide formation from sterigmatocystin and drug-metabolizing enzymes in the liver microsome.

来源:Hazardous Substances Data Bank (HSDB)

代谢

/杂色曲霉素/是由/人类P450酶，CYP3A4/激活的。/根据表格/

/Sterigmatocystin is/ activated by /a/ human P450 enzyme, CYP3A4. /From table/

来源:Hazardous Substances Data Bank (HSDB)

代谢

主要尿代谢物被鉴定为sterigmatocystin-beta-D-葡萄糖苷酸。另一种代谢物是1,2-二氢-2-(N7-鸟嘌呤基)-1-羟基sterigmatocystin。

The major urinary metabolite is identified as sterigmatocystin-beta-d-glucuronide. Another metabolite is 1,2-dihydro-2-(N7-guanyl)-1-hydroxysterigmatocystin. (A2889, A2890)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

杂色曲霉素的致癌性质是由于其能够形成鸟嘌呤DNA加合物并与DNA结合。此外，DNA加合物的形成导致活性氧种类的产生增加和抗氧化防御的失衡，进而增强脂质过氧化，造成细胞损伤。

Sterigmatocystin's carcinogenic properties are a result of its ability to form guanyl DNA adducts and bind to DNA. In addition, DNA adduct formation causes enhanced production of reactive oxygen species and an imbalance in antioxidant defense, leading to enhanced lipid peroxidation that causes cell damage. (A2888, A2958, A2959)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌性证据

没有关于人类的数据。有充分的证据表明对动物具有致癌性。总体评估：2B组：该物质可能对人类具有致癌性。

No data are available in humans. Sufficient evidence of carcinogenicity in animals. OVERALL EVALUATION: Group 2B: The agent is possibly carcinogenic to humans.

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：杂色曲霉素

IARC Carcinogenic Agent:Sterigmatocystin

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)

毒理性

• 致癌物分类

国际癌症研究机构专著：第10卷：（1976年）一些天然存在的物质

IARC Monographs:Volume 10: (1976) Some Naturally Occurring Substances

来源:International Agency for Research on Cancer (IARC)

吸收、分配和排泄

在大鼠单次腹腔注射6.4毫克/动物(14)C-杂色曲霉素（DMSO为溶剂）后，12小时内在尿液中发现了5.6%的活性，在大肠和肠道中发现了67%，在肝脏中发现了11%。这些水平在24小时后略有下降。在禁食或非禁食的大鼠口服1.4毫克/动物(3)H-杂色曲霉素后，16小时内在粪便和肠道中发现了最高的活性；在尿液、血液、呼出空气、肝脏和肾脏中发现了较少的量。

In rats given a single ip injection of 6.4 mg/animal (14)C-sterigmatocystin in DMSO, 5.6% of the activity was found in the urine, 67% in the feces and GI tract and 11% in the liver after 12 hours. These levels declined slightly after 24 hr. In fasted or non-fasted rats given 1.4 mg/animal (3)H-sterigmatocystin orally, the highest activity after 16 hr was found in the feces and GI tract; lesser amounts were found in the urine, blood, expired air, liver and kidneys.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1(b)
• 危险品标志：
  T
• 安全说明：
  S36/37,S45
• 危险类别码：
  R25
• WGK Germany：
  3
• 海关编码：
  2932999099
• 危险品运输编号：
  UN 3462 6
• RTECS号：
  LV1750000
• 包装等级：
  III
• 危险类别：
  6.1(b)
• 储存条件：
  存放在0 ºC以下阴凉干燥的环境中，并充氩密封。

SDS

Name:	Sterigmatocystin Material Safety Data Sheet
Synonym:
CAS:	10048-13-2

Section 1 - Chemical Product MSDS Name:Sterigmatocystin Material Safety Data Sheet
Synonym:

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
10048-13-2	Sterigmatocystin	ca 100	233-158-6

Hazard Symbols: T
Risk Phrases: 23/24/25 40

---

Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Toxic by inhalation, in contact with skin and if swallowed. Limited evidence of a carcinogenic effect.
Potential Health Effects
Eye:
May cause eye irritation.
Skin:
May cause skin irritation.
Ingestion:
Harmful if swallowed. May cause irritation of the digestive tract.
May cause liver and kidney damage.
Inhalation:
May cause respiratory tract irritation. The toxicological properties of this substance have not been fully investigated.
Chronic:
May cause liver and kidney damage. May cause cancer according to animal studies.

---

Section 4 - FIRST AID MEASURES
Eyes: Flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid.
Skin:
Get medical aid. Flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes. Wash clothing before reuse.
Ingestion:
Get medical aid. Do NOT induce vomiting. If conscious and alert, rinse mouth and drink 2-4 cupfuls of milk or water.
Inhalation:
Remove from exposure and move to fresh air immediately. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical aid.
Notes to Physician:

---

Section 5 - FIRE FIGHTING MEASURES
General Information:
As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear. During a fire, irritating and highly toxic gases may be generated by thermal decomposition or combustion.
Extinguishing Media:
Use agent most appropriate to extinguish fire. Use water spray, dry chemical, carbon dioxide, or appropriate foam.

---

Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Vacuum or sweep up material and place into a suitable disposal container. Clean up spills immediately, observing precautions in the Protective Equipment section. Avoid generating dusty conditions.
Provide ventilation.

---

Section 7 - HANDLING and STORAGE
Handling:
Wash thoroughly after handling. Use with adequate ventilation.
Minimize dust generation and accumulation. Avoid contact with eyes, skin, and clothing. Keep container tightly closed. Avoid ingestion and inhalation.
Storage:
Store in a tightly closed container. Store in a cool, dry, well-ventilated area away from incompatible substances.

---

Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION
Engineering Controls:
Facilities storing or utilizing this material should be equipped with an eyewash facility and a safety shower. Use adequate ventilation to keep airborne concentrations low.
Exposure Limits CAS# 10048-13-2: Personal Protective Equipment Eyes: Wear appropriate protective eyeglasses or chemical safety goggles as described by OSHA's eye and face protection regulations in 29 CFR 1910.133 or European Standard EN166.
Skin:
Wear appropriate protective gloves to prevent skin exposure.
Clothing:
Wear appropriate protective clothing to prevent skin exposure.
Respirators:
A respiratory protection program that meets OSHA's 29 CFR 1910.134 and ANSI Z88.2 requirements or European Standard EN 149 must be followed whenever workplace conditions warrant respirator use.

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Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Crystals
Color: yellow crystalline powder
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Decomposes
Freezing/Melting Point: 240 - 246 deg C
Autoignition Temperature: Not applicable.
Flash Point: Not applicable.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature: > 246 deg C
Solubility in water: Insoluble.
Specific Gravity/Density:
Molecular Formula: C18H12O6
Molecular Weight: 324.28

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable at room temperature in closed containers under normal storage and handling conditions.
Conditions to Avoid:
Incompatible materials, dust generation, excess heat.
Incompatibilities with Other Materials:
Oxidizing agents.
Hazardous Decomposition Products:
Carbon monoxide, irritating and toxic fumes and gases, carbon dioxide.
Hazardous Polymerization: Has not been reported

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 10048-13-2: LV1750000 LD50/LC50:
CAS# 10048-13-2: Oral, mouse: LD50 = >800 mg/kg; Oral, rat: LD50 = 120 mg/kg.
Carcinogenicity:
Sterigmatocystin - California: carcinogen, initial date 4/1/88 IARC: Group 2B carcinogen Other:
See actual entry in RTECS for complete information.

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Section 12 - ECOLOGICAL INFORMATION

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Section 13 - DISPOSAL CONSIDERATIONS
Dispose of in a manner consistent with federal, state, and local regulations.

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Section 14 - TRANSPORT INFORMATION

IATA
Shipping Name: TOXIC SOLID, ORGANIC, N.O.S.*
Hazard Class: 6.1
UN Number: 2811
Packing Group: III
IMO
Shipping Name: TOXIC SOLID, ORGANIC, N.O.S.
Hazard Class: 6.1
UN Number: 2811
Packing Group: III
RID/ADR
Shipping Name: TOXIC SOLID, ORGANIC, N.O.S.
Hazard Class: 6.1
UN Number: 2811
Packing group: III

---

Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: T
Risk Phrases:
R 23/24/25 Toxic by inhalation, in contact with skin
and if swallowed.
R 40 Limited evidence of a carcinogenic effect.
Safety Phrases:
S 28A After contact with skin, wash immediately with
plenty of water.
S 36/37/39 Wear suitable protective clothing, gloves
and eye/face protection.
S 37 Wear suitable gloves.
S 38 In case of insufficient ventilation, wear
suitable respiratory equipment.
S 45 In case of accident or if you feel unwell, seek
medical advice immediately (show the label where
possible).
WGK (Water Danger/Protection)
CAS# 10048-13-2: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 10048-13-2 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 10048-13-2 is not listed on the TSCA inventory.
It is for research and development use only.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

概述

柄曲霉素又称为杂色曲霉素。杂色曲霉素（Sterigmatocystin，ST）是一种致癌、致畸的真菌毒素，是黄曲霉毒素（Aflatoxin，AFT）的合成前体，两者结构相似，均由双呋喃环与氧杂蒽醌连接组成。ST被国际癌症研究机构归类为2B类致癌物质，并与肺癌、肝癌及胃癌密切相关。

特性

杂色曲霉素（Sterigmatocystin 简称ST）是一种具有强烈肝脏和肾脏毒性的杂环化合物，能够诱发多种肿瘤。在南非某些地区的高发肝癌可能与此有关。这种毒素可导致胆管癌和肝癌，虽有致突变作用，但对食品的污染频率较低。此外，ST还能转化为更强烈的致癌物质——黄曲霉毒素，并且还会引起一些动物疾病。

生物活性

Sterigmatocystin 是黄曲霉素的前体，由Aspergillus versicolor产生的一种霉菌素。它是一种G1期和DNA合成的抑制剂，用于抑制p21的活性。Sterigmatocystin 对动物发育具有致畸性和致癌作用。

体外研究

Sterigmatocystine 引起的DNA损伤激活了ATM/53依赖性信号通路，在GES-1细胞中诱导G2期停滞。

体内研究

Sterigmatocystine（腹腔注射；每天3毫克/公斤，持续14天）抑制p21^WAF1/CIP1。

类别

有毒物质

毒性分级：高毒

急性毒性

• 大鼠：口服LD50 120毫克/公斤
• 小鼠：口服LD50 >800毫克/公斤

可燃性危险特性

• 易燃，火场排出辛辣刺激烟雾

储运特性

• 库房低温、通风、干燥
• 与食品原料分开存放

灭火剂

• 水
• 二氧化碳
• 泡沫
• 沙土

反应信息

• 作为反应物：
  描述：

  sterigmatocystin 在 palladium on activated charcoal 氢气 、 sodium hydride 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 1,2-二氢-O-甲基杂色曲霉毒素
  参考文献：
  名称：

  在去甲基异形囊藻毒素形成过程中对还原性和细胞色素 P450 氧化步骤进行排序，从而对黄曲霉毒素和相关真菌代谢物的生物合成进行全面了解

  摘要：

  强环境致癌物黄曲霉毒素 B1 的生物合成涉及约。超出第一个聚酮化合物中间体 15 个步骤。其中的核心是蒽醌杂色素 A 重排为氧杂蒽酮去甲基杂色藻素。遗传证据强烈表明该过程需要两种酶，细胞色素 P450 AflN 和可能依赖 NADPH 的氧化还原酶 AflM。鉴于此骨架重排中明显的整体氧化还原变化，必然会发生两轮氧化和还原。早期的实验表明，杂色素 A 的还原脱氧不是第一步。在本报告中，我们考虑了一种机制替代方案，即 AflM 介导的还原是在形成呫吨酮中间体之前这三个反应中的最后一个。为此，9-羟基二氢去甲基sterigmatocystin 及其9-脱氧类似物（一种已建立的黄曲霉毒素前体）是通过全合成制备的。在“角形”合成氧杂蒽酮靶的最终分离过程中，发现酸催化促进它们的异构化为热力学有利的“线性”氧杂蒽酮。9-羟基-和9-脱氧氧杂蒽酮的全细胞和地面细胞孵育是用在该途径的第一步阻断的寄生曲霉突

  DOI：

  10.1021/ja0455188

文献信息

• COMPOUNDS FOR INHIBITION OF FUNGAL MYCOTOXIN AND SPORULATION
  申请人：Strasburg Gale M.

  公开号：US20180192648A1

  公开（公告）日：2018-07-12

  Compounds and compositions are described herein that inhibit the biosynthesis of mycotoxins and fungal sporulation. Such compounds and compositions are useful for inhibiting mold. Methods of using such compounds and compositions are also described herein that involve applying the compositions to plants, plant parts, structures, containers, and other surfaces.

  本文描述了一些化合物和组合物，可以抑制霉菌毒素的生物合成和真菌孢子的形成。这些化合物和组合物对于抑制霉菌非常有用。本文还描述了使用这些化合物和组合物的方法，包括将它们应用于植物、植物部分、结构、容器和其他表面。
• 4,7-Diazaindole derivatives and their use as fungicides
  申请人：Bayer CropScience AG

  公开号：EP2338890A1

  公开（公告）日：2011-06-29

  The present invention relates to compounds of formula (I) their process of preparation, their use for preventing and/or controlling fungal infection in plants and/or plant propagation material and for reducing mycotoxin contamination in plants or plant material, and compositions containing these compounds.

  本发明涉及式(I)化合物及其制备方法，用于预防和/或控制植物和/或植物繁殖材料的真菌感染，以及减少植物或植物材料中霉菌毒素污染的用途，以及含有这些化合物的组合物。
• Lipoxygenase genes, promoters, transit peptides and proteins thereof
  申请人：——

  公开号：US20040103453A1

  公开（公告）日：2004-05-27

  This invention describes novel lipoxygenase genes and promoters, transit peptides and proteins derived therefrom. More specifically, this invention describes novel promoters that confer chemically inducible but not wound- or pathogen-inducible expression to an associated nucleotide sequence. The invention further describes peptides capable of targeting and associated protein to plastids and proteins having lipoxygenase activity which can be used to inhibit fungal mycotoxins. The invention also describes recombinant sequences containing such promoter sequences, and/or sequences encoding transit peptides and proteins according to the invention. The said recombinant DNA sequences may be used to create transgenic plants, but especially transgenic plants expressing a nucleotide sequence of interest in response to chemicals but not in response to wounding or pathogens.

  本发明描述了新型的脂氧合酶基因和启动子、转运肽和由此衍生的蛋白质。更具体地，本发明描述了赋予化学诱导但不是伤口或病原体诱导表达与相关核苷酸序列相关的新型启动子。该发明还描述了能够将相关蛋白质定向到质体的肽和具有脂氧合酶活性的蛋白质，可用于抑制真菌毒素。该发明还描述了包含此类启动子序列和/或根据本发明编码转运肽和蛋白质的序列的重组序列。这些重组DNA序列可用于创建转基因植物，尤其是在对化学物质做出反应但不对伤口或病原体做出反应的转基因植物表达感兴趣的核苷酸序列。
• NOVEL CELL WALL DECONSTRUCTION ENZYMES OF SCYTALIDIUM THERMOPHILUM, MYRIOCOCCUM THERMOPHILUM, AND AUREOBASIDIUM PULLULANS, AND USES THEREOF
  申请人：CONCORDIA UNIVERSITY

  公开号：US20150175980A1

  公开（公告）日：2015-06-25

  The present invention relates to novel polypeptides and enzymes (e.g., thermostable proteins and enzymes) having activities relating to biomass processing and/or degradation (e.g., cell wall deconstruction), as well as polynucleotides, vectors, cells, compositions and tools relating to same, or functional variants thereof. More particularly, the present invention relates to secreted enzymes that may be isolated from the fungi, Scytalidium thermophilum strain CBS 625.91, Myriococcum thermophilum strain CBS 389.93, and Aureobasidium pullulans strain ATCC 62921. Uses thereof in various industrial processes such as in biofuels, food preparation, animal feed, pulp and paper, textiles, detergents, waste treatment and others are also disclosed.

  本发明涉及与生物质加工和/或分解（例如，细胞壁分解）相关的活性的新型多肽和酶（例如，热稳定蛋白和酶），以及与之相关的多核苷酸、载体、细胞、组合物和工具，或其功能变体。更具体地说，本发明涉及可从真菌Scytalidium thermophilumstrain CBS 625.91、Myriococcum thermophilumstrain CBS 389.93和Aureobasidium pullulansstrain ATCC 62921中分离的分泌酶。还公开了这些酶在各种工业过程中的用途，例如生物燃料、食品制备、动物饲料、纸浆和纸张、纺织品、洗涤剂、废物处理等。
• Präparat zur Wirkstoffapplikation in Kleinsttröpfchenform
  申请人：Cevc, Gregor, Prof. Dr.

  公开号：EP0475160A1

  公开（公告）日：1992-03-18

  Die Erfindung betrifft ein Präparat zur Applikation von Wirkstoffen in Form kleinster, insbesondere mit einer membranartigen Hülle aus einer oder wenigen Lagen amphiphiler Moleküle bzw. mit einer amphiphilen Trägersubstanz versehenen Flüssigkeitströpfchen, insbesondere zum Transport des Wirkstoffes in und durch natürliche Barrieren und Konstriktionen wie Häute und dergleichen. Das Präparat weist einen Gehalt einer randaktiven Substanz auf, der bis zu 99 Mol.-% des Gehaltes dieser Substanz entspricht, durch den der Solubilisierungspunkt der Tröpfchen erreicht wird. Das Präparat eignet sich zur nichtinvasiven Verabreichung von Antidiabetica, insbesondere von Insulin. Die Erfindung betrifft außerdem ein Verfahren zur Herstellung solcher Präparate.

  本发明涉及一种以微小液滴形式施用活性物质的制剂，特别是具有一层或几层两亲性分子或两亲性载体物质的膜状包膜，尤其是用于将活性物质输送到或通过皮肤等天然屏障和收缩物。制剂中边缘活性物质的含量最高可达 99 摩尔%，从而达到液滴的溶解点。该制剂适用于非侵入性给药抗糖尿病药物，特别是胰岛素。本发明还涉及生产这种制剂的工艺。