penicillic acid | 90-65-3

• 物质功能分类: 化学试剂 - 有机试剂 - 脂肪酸
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: penicillic acid
• 英文别名: (2E)-3-methoxy-5-methyl-4-oxohexa-2,5-dienoic acid
• CAS: 90-65-3
• 化学式: C₈H₁₀O₄
• 分子量: 170.165
• InChiKey: VOUGEZYPVGAPBB-GQCTYLIASA-N

物化性质

• 熔点：
  83-87 °C
• 沸点：
  219.79°C (rough estimate)
• 密度：
  1.1456 (rough estimate)
• 溶解度：
  二甲基亚砜：>10mg/mL
• 颜色/状态：
  NEEDLES FROM PETROLEUM ETHER
• 分解：
  When heated to decomposition it emits acrid smoke and irritating fumes.

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

ADMET

代谢

青霉素酸是已知与蓝纹奶酪相关的青霉菌菌株的代谢产物。

PENICILLIC ACID IS A KNOWN METABOLITE OF STRAINS OF PENICILLIUM ROQUEFORTI ASSOCIATED WITH BLUE-VEINED CHEESES.

来源:Hazardous Substances Data Bank (HSDB)

代谢

百分之十的青霉素酸代谢物在小鼠雄性中检测为葡萄糖醛酸苷结合物。尿液、血浆和胆汁中的所有代谢物都比原化合物更具极性。主要的代谢物是谷胱甘肽或半胱氨酸的结合物或衍生物。

TEN PERCENT OF PENICILLIC ACID METABOLITES IN MALE MICE WERE DETECTED AS GLUCURONIDE CONJUGATES. ALL METABOLITES IN URINE, PLASMA AND BILE WERE MORE POLAR THAN THE PARENT COMPOUND. THE MAJOR METABOLITES WERE CONJUGATES OR DERIVATIVES OF GLUTATHIONE OR CYSTEINE.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在小鼠肝脏匀浆的亚细胞组分中，青酸与谷胱甘肽发生酶促和非酶促反应；每个反应都同等重要。当没有谷胱甘肽时，各种肝脏亚细胞组分的新陈代谢基本上是非酶促的，但是当谷胱甘肽可用时，新陈代谢增加了。在谷胱甘肽的存在下，30分钟内添加的青酸有75%被生物转化为不能被有机溶剂提取且比青酸极性更大的代谢物。

IN SUBCELLULAR FRACTIONS OF MOUSE LIVER HOMOGENATES, PENICILLIC ACID REACTS WITH GLUTATHIONE BOTH ENZYMICALLY AND NONENZYMICALLY; EACH REACTION WAS OF EQUAL IMPORTANCE. METABOLISM BY VARIOUS HEPATIC SUBCELLULAR FRACTIONS WAS ESSENTIALLY NONENZYMIC WHEN GLUTATHIONE WAS ABSENT, BUT METABOLISM WAS INCREASED WHEN GLUTATHIONE WAS AVAILABLE. IN THE PRESENCE OF GLUTATHIONE, 75% OF ADDED PENICILLIC ACID WAS BIOTRANSFORMED WITHIN 30 MINUTES TO METABOLITES NOT EXTRACTABLE WITH ORGANIC SOLVENTS AND MORE POLAR THAN PENICILLIC ACID.

来源:Hazardous Substances Data Bank (HSDB)

代谢

青霉素酸在肝脏中被迅速吸收并广泛代谢。通过谷胱甘肽S-转移酶的相互作用发生解毒，代谢物主要通过尿液排出。(A3011, A3013)

Penicillic acid is rapidly absorbed and extensively metabolized in the liver. Detoxification occurs via interactions with glutathione S-transferases and metabolites are excreted mainly in the urine. (A3011, A3013)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性总结

青霉素酸已被证明通过在酶活性位点的半胱氨酸或赖氨酸残基上形成共价加合物来抑制醇脱氢酶和乳糖脱氢酶。青霉素酸还直接与半胱天冬酶-8大亚基的活性中心半胱氨酸结合，从而通过靶向半胱天冬酶-8的自我加工来抑制FasL诱导的凋亡。青霉素酸还具有诱变性，可以引起DNA单链断裂、染色体畸变和DNA合成抑制。霉菌毒素通常能够通过人类有机阴离子转运体（hOATs）和人类有机阳离子转运体（hOCTs）进入肝脏和肾脏。它们还可以抑制这些转运体对阴离子和阳离子的摄取，干扰内源性代谢物、药物和外源性物质（包括它们自身）的分泌。这导致细胞内毒性化合物的积累增加，引起肾毒性和肝毒性。（A2957, A3007, A3008, A3010, A3012, A3014）

Penicillic acid has been shown to inhibit alcohol and lactate dehydrogenases by forming covalent adducts with either cysteine or lysine residues at the enzyme active sites. Penicillic acid also binds directly to the active center cysteine in the large subunit of caspase-8, thus inhibiting FasL-induced apoptosis by targeting self-processing of caspase-8. Penicillic acid is also mutagenic and can cause DNA single-strand breaks, chromosome aberrations, and inhibition of DNA synthesis. Mycotoxins are often able to enter the liver and kidney by human organic anion transporters (hOATs) and human organic cation transporters (hOCTs). They can also inhibit uptake of anions and cations by these transporters, interefering with the secretion of endogenous metabolites, drugs, and xenobiotics including themselves. This results in increased cellular accumulation of toxic compounds causing nephro- and hepatotoxicity. (A2957, A3007, A3008, A3010, A3012, A3014)

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。动物致癌性证据有限。总体评估：第3组：该物质对人类致癌性无法分类。

No data are available in humans. Limited evidence of carcinogenicity in animals. OVERALL EVALUATION: Group 3: The agent is not classifiable as to its carcinogenicity 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剂：青霉酸

IARC Carcinogenic Agent:Penicillic acid

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：第3组：无法归类其对人类致癌性

IARC Carcinogenic Classes:Group 3: Not classifiable as to its carcinogenicity 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

体内和体外研究表明，红血细胞对(14)C-青霉酸的摄取显著，随着时间的推移（1-4小时），与膜组分相关的放射性活性显著增加。然而，大部分的血细胞活性是在细胞内的。肝脏组分中的(14)C放射性浓度占RNA-DNA和蛋白质组分的1.5%。与这些组分相关的(14)C活性的水平随着时间的推移（24小时）而增加。对大鼠体内[(14)C]青霉酸代谢的研究表明，大量的放射性物质通过尿液排出（7天后占给药剂量的82%）。给药后2小时，胆汁代谢物占给药剂量的10%。

IN VIVO AND IN VITRO STUDIES SHOWED SIGNIFICANT UPTAKE OF (14)C-PENICILLIC ACID BY RED BLOOD CELLS AND A SIGNIFICANT INCREASE IN RADIOACTIVITY ASSOCIATED WITH THE MEMBRANE FRACTION WITH TIME (1-4 HOURS). HOWEVER, THE MAJORITY OF THE BLOOD CELL ACTIVITY WAS INTRACELLULAR. THE (14)C-RADIOACTIVITY CONCENTRATION IN LIVER FRACTIONS (1.5% OF THE RNA-DNA AND PROTEIN FRACTIONS. THE LEVEL OF THE (14)C ACTIVITY ASSOCIATED WITH THESE FRACTIONS INCREASED WITH TIME (24 HR). STUDIES OF THE IN VIVO METABOLISM OF [(14)C] PENICILLIC ACID BY RATS SHOWED THAT A SIGNIFICANT AMOUNT OF RADIOACTIVITY WAS EXCRETED IN THE URINE (82% OF THE ADMINISTERED DOSE AFTER 7 DAYS). BILIARY METABOLITES ACCOUNTED FOR 10% OF ADMINISTERED DOSE 2 HOURS AFTER ADMINISTRATION.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1(b)
• 危险品标志：
  Xn,T
• 安全说明：
  S24/25,S26,S37/39
• 危险类别码：
  R36/37/38
• 海关编码：
  2918990090
• 危险品运输编号：
  UN 2811
• 包装等级：
  III
• 危险类别：
  6.1(b)

制备方法与用途

青霉酸是什么

青霉酸（penicillic acid）主要在软毛青霉中合成，是一种由圆弧青霉菌产生的代谢产物，在饲料中的最高含量可达到2%。这种毒素是危害养殖业的常见霉菌之一，长期饲喂含青霉酸的饲料能使动物肝脏肿大、肝细胞变性，并抑制动物细胞DNA合成；严重的甚至会导致动物细胞DNA断裂。此外，青霉酸与其他霉菌毒素共同作用时还会产生联合毒性。

青霉酸（PA）是由Alsberg和Black在1913年发现并命名的，主要在软毛青霉中合成的一种青霉毒素。它广泛存在于许多农产品中，如玉米、干豆、动物饲料等。研究发现，过量摄入PA会引起多种毒性症状，包括肝毒性、细胞毒性和肺泡毒性，并且具有致癌作用。通过食物链富集的PA对人体健康构成威胁，因此建立一套行之有效的快速检测方法非常重要。

青霉酸的主要用途

青霉酸主要是由曲霉菌和青霉菌产生的次级代谢产物，拥有广泛的生物活性。

青霉酸的生物活性

Penicillic acid 是一种聚酮化合物霉菌毒素，在体外对大鼠肺泡巨噬细胞 (AM) 具有细胞毒性。它通过阻断 caspase-8 自我加工来抑制 Fas 配体诱导的细胞凋亡。

类别：有毒物质
毒性分级：高毒
急性毒性：腹腔—大鼠 LD50 90 毫克/公斤；口服—小鼠 LD50: 600 毫克/公斤
可燃性危险特性：可燃，火场排出辛辣刺激烟雾
储运特性：库房低温、通风、干燥
灭火剂：水、二氧化碳、干粉、砂土

文献信息

• [EN] KETAL ESTERS OF ANHYDROPENTITOLS AND USES THEREOF<br/>[FR] CÉTO-ESTERS D'ANHYDROPENTITOLS ET LEURS UTILISATIONS
  申请人：XLTERRA INC

  公开号：WO2010138842A1

  公开（公告）日：2010-12-02

  The present disclosure relates to the preparation of ketal compounds from anhydropentitols and oxocarboxylates; derivatives, homopolymers, and copolymers thereof; and various compositions, formulations, and articles derived therefrom.

  本公开涉及从无水戊糖醇和羰基羧酸酯制备缩酮化合物；以及它们的衍生物、同聚物和共聚物；以及由此衍生的各种组合物、配方和制品。
• [EN] METHOD OF MAKING KETALS AND ACETALS<br/>[FR] PROCÉDÉ DE FABRICATION DE CÉTALS ET D'ACÉTALS
  申请人：SEGETIS INC

  公开号：WO2009048874A1

  公开（公告）日：2009-04-16

  The reaction of alcohols with oxocarboxylates to form acetals or ketals is catalyzed by unexpectedly low levels of protic acids. By employing low acid catalyst levels compared to amounts conventionally used, rapid formation of acetal or ketal is facilitated while the formation of oxocarboxylate esters is minimized. Further employing a significant molar excess of oxocarboxylate in conjunction with low acid catalyst level gives rise to the rapid and clean formation of acetals and ketals from oxocarboxylates and alcohols.

  醇与羰基羧酸酯反应形成缩醛或缩酮，其催化剂是意外地低水平的质子酸。通过使用比传统用量低的酸催化剂水平，促进了缩醛或缩酮的快速形成，同时最小化了羰基羧酸酯的形成。进一步采用大量的羰基羧酸酯与低水平酸催化剂结合，可以使羰基羧酸酯和醇快速而干净地形成缩醛和缩酮。
• TOPICAL FORMULATIONS
  申请人：BECK Petra Helga

  公开号：US20100093691A1

  公开（公告）日：2010-04-15

  There is provided topical pharmaceutical compositions comprising compounds of formula I wherein R 1 , R 2 , R 3 and X have meanings given in the description. These compositions can be used to treat microbial infections and to kill clinically latent microorganisms.

  提供了一种含有I式化合物的局部制药组合物，其中R1、R2、R3和X的含义在说明中给出。这些组合物可用于治疗微生物感染并杀死临床潜伏微生物。
• SOLVENT, SOLUTION, CLEANING COMPOSITION AND METHODS
  申请人：Rieth Lee R.

  公开号：US20120128614A1

  公开（公告）日：2012-05-24

  A cleaning composition can comprise aqueous, nonaqueous liquid, or solid formulations The formulations can contain a surfactant and a solvent The solvent has been shown to have utility in promoting removal, solubilizing or cleaning undesirable soil residues from a number of substrates The solvent materials can be used as a component of an aqueous solution, can be combined in a solid or powdered formulation as an encapsulated solvent or can be combined in a solid or powdered formulation as a solvent absorbed on a solid earner The aqueous formulations can be made in the form of a concentrate The cleaner can be combined with water to form an active cleaning solution that can be applied in a variety of cleaning processes The cleaner can contain additional ingredients including surfactants, builders, sequestrates, bleaches, biocides, to be found in cleaners of general and specific applications Personal care cleaning products are also described.

  清洁剂可以包括水性、非水性液体或固体配方。这些配方可以包含表面活性剂和溶剂。已经证明，溶剂在促进从多种基质中去除、溶解或清洁不良土壤残留物方面具有实用性。溶剂材料可以作为水溶液的组分使用，可以作为封装溶剂的固体或粉末配方结合使用，也可以作为吸附在固体载体上的溶剂的固体或粉末配方结合使用。水性配方可以制成浓缩液的形式。清洁剂可以与水混合形成活性清洁溶液，可应用于各种清洁过程。清洁剂可以包含其他成分，包括表面活性剂、建筑材料、螯合剂、漂白剂、生物杀灭剂，以满足一般和特定应用领域的清洁剂的需求。还描述了个人护理清洁产品。
• USE OF PYRROLOQUINOLINE COMPOUNDS TO KILL CLINICALLY LATENT MICROORGANISMS
  申请人：Beck Petra Helga

  公开号：US20120231995A1

  公开（公告）日：2012-09-13

  There is provided the use of compounds of formula I wherein R 1 , R 2 , R 3 and X have meanings given in the description, for the preparation of a medicament for killing clinically latent microorganisms. There is also provided the use of compounds of formula I for treating microbial infections, as well as certain compounds of formula I per se.

  提供了使用式子I中的化合物，其中R1、R2、R3和X的含义在说明中给出，用于制备杀死临床潜伏微生物的药物。还提供了使用式子I中的化合物治疗微生物感染的方法，以及某些式子I中的化合物本身。