N''-[(E)-2-(4-Chlorophenoxy)ethanoyl]-N-(4,7-dimethyl-2-quinazolinyl)guanidine | 21259-20-1

• 物质功能分类: 分析化学 - 标准品 - 食品和化妆品标准品
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: N''-[(E)-2-(4-Chlorophenoxy)ethanoyl]-N-(4,7-dimethyl-2-quinazolinyl)guanidine
• 英文别名: [(1S,10R,11S,12S)-11-acetyloxy-2-(acetyloxymethyl)-10-hydroxy-1,5-dimethylspiro[8-oxatricyclo[7.2.1.02,7]dodec-5-ene-12,2'-oxirane]-4-yl] 3-methylbutanoate
• CAS: 21259-20-1
• 化学式: C₂₄H₃₄O₉
• 分子量: 466.5
• InChiKey: BXFOFFBJRFZBQZ-BJDCVSBTSA-N

物化性质

• 熔点：
  151.5℃
• 比旋光度：
  D26 +15° (c = 2.58 in ethanol)
• 沸点：
  489.35°C (rough estimate)
• 密度：
  1.1942 (rough estimate)
• 闪点：
  2 °C
• 溶解度：
  DMF：30mg/mL； DMSO：30mg/mL； DMSO:PBS(pH7.2)(1:1)：0.5mg/ml；乙醇：20mg/mL
• 颜色/状态：
  White needles from benzene & Skellysolve B; acetate deriv: amorphous solid from ether & pentane
• 蒸汽压力：
  3.06X10-11 mm Hg at 25 °C (est)
• 稳定性/保质期：
  Stable in the solid form
• 旋光度：
  Specific optical rotation: (c = 2.58 in ethanol): +15 °C at 26 °C/D
• 分解：
  Hazardous decomposition products formed under fire conditions. - Carbon oxides
• 保留指数：
  2822;2815.5

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  121
• 氢给体数：
  1
• 氢受体数：
  9

ADMET

代谢

给一头哺乳期母牛口服180毫克T-2毒素后，从其尿液中获得了两种主要代谢物。它们是3'-羟基-HT 2毒素和3'-羟基T 2毒素。

Two major metabolites were obtained from the urine of a lactating cow given 180 mg of T-2 toxin orally. They were 3'-hydroxy-HT 2 toxin & 3'-hydroxy T 2 toxin.

来源:Hazardous Substances Data Bank (HSDB)

代谢

人类肝脏酶在体外将T2-三线镰刀菌毒素去乙酰化成HT2-三线镰刀菌毒素。

Human liver enzymes deacetylate T2-trichothecene to HT2-trichothecene in vitro.

来源:Hazardous Substances Data Bank (HSDB)

代谢

口服给予小鼠和大鼠(3)H-T2-三线霉素(1 mg/kg体重)的放射性，在72小时内以粪便(55%)和尿液(15%)的形式回收。 ... 分析大鼠粪便中回收的放射性，发现剂量的2.7%以未改变的T2-三线霉素形式排出，7.5%以4-O-脱乙酰化T2-三线霉素(HT2-三线霉素)形式排出...其余的粪便排泄产物未鉴定。 在尿液中，鉴定出HT2-三线霉素，占总剂量的1.4%，以及8-羟基二乙酰氧基斯卡波醇(1.8%)；还分离出3种未鉴定的代谢物...。 环氧基团...似乎是其毒理学活性的关键；肝脏通过环氧水合酶可能对T2-三线霉素进行解毒。 在体外，大鼠肝脏匀浆将T2-三线霉素代谢为HT2-三线霉素、T2-三线霉素四醇、4-脱乙酰新鞘醇...和新鞘醇... 从HT2-三线霉素也得到了相同的代谢物，表明T2-三线霉素优先在C-4位置水解，生成NT2-三线霉素。

The radioactivity of orally admin (3)H-T2-trichothecene (1 mg/kg body wt) to mice & rats was recovered in feces (55%) & urine (15%) within 72 hr. ... Analysis of the radioactivity recovered in feces of rats revealed that 2.7% of the dose was excreted as unchanged T2-trichothecene & 7.5% as 4-O-deacetylated T2-trichothecene (HT2-trichothecene)...the remaining fecal excretion products were not identified. In urine, HT2-trichothecene, representing 1.4% of the total dose & 8-hydroxydiacetoxyscirpenol (1.8%) were identified; 3 unidentified metabolites...were also isolated. The epoxide moeity...seems to be essential for its toxicological activity; the liver detoxifies T2-trichothecene, probably through epoxide hydrolase. In vitro, rat liver homogenate metabolizes T2-trichothecene to HT2-trichothecene, T2-trichothecene tetraol, 4-deacetylneosolaniol...& neosolaniol... The same metabolites were obtained from HT2-trichothecene, indicating that T2-trichothecene was preferentially hydrolyzed at the C-4 position to give NT2-trichothecene.

来源:Hazardous Substances Data Bank (HSDB)

代谢

曲霉菌属产生的三环烯类是倍半萜类毒素。由于这些霉菌毒素非常稳定，因此对微生物转化以去除受污染的谷物或谷物产品中的毒素产生了兴趣。对23种酵母菌进行了测试，这些酵母菌被归类到毛霉科（子囊菌门，担子菌纲），包括四种毛霉属和19种目前归类在芽孢毛霉属的无性型物种，以测试它们将三环烯T-2毒素转化为较少毒性产物的能力。这些物种产生了三种生物转化类型：乙酰化形成3-乙酰T-2毒素，糖基化形成T-2毒素3-葡萄糖苷，以及去除异戊酰基团形成新毒素。一些物种产生了多种生物转化类型。三种芽孢毛霉属物种将T-2毒素转化为T-2毒素3-葡萄糖苷，这种化合物已被识别为受曲霉感染谷物中的隐蔽霉菌毒素。这是首次报告微生物全细胞方法用于生产三环烯糖苷，T-2毒素3-葡萄糖苷的大规模可用性将促进毒性测试和开发检测农业和其他产品中这种化合物的方法。

Trichothecenes are sesquiterpenoid toxins produced by Fusarium species. Since these mycotoxins are very stable, there is interest in microbial transformations that can remove toxins from contaminated grain or cereal products. Twenty-three yeast species assigned to the Trichomonascus clade (Saccharomycotina, Ascomycota), including four Trichomonascus species and 19 anamorphic species presently classified in Blastobotrys, were tested for their ability to convert the trichothecene T-2 toxin to less-toxic products. These species gave three types of biotransformations: acetylation to 3-acetyl T-2 toxin, glycosylation to T-2 toxin 3-glucoside, and removal of the isovaleryl group to form neosolaniol. Some species gave more than one type of biotransformation. Three Blastobotrys species converted T-2 toxin into T-2 toxin 3-glucoside, a compound that has been identified as a masked mycotoxin in Fusarium-infected grain. This is the first report of a microbial whole-cell method for producing trichothecene glycosides, and the potential large-scale availability of T-2 toxin 3-glucoside will facilitate toxicity testing and development of methods for detection of this compound in agricultural and other products.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

评估：没有关于来自串珠镰刀菌的毒素对人类致癌性的数据。T-2毒素在实验动物中的致癌性有有限证据。总体评估：来自串珠镰刀菌的毒素对人类的致癌性无法分类（第3组）。

Evaluation: No data were available on the carcinogenicity to humans of toxins derived from Fusarium sporotrichioides. There is limited evidence in experimental animals for the carcinogenicity of T-2 toxin. Overall evaluation: Toxins derived from Fusarium sporotrichiodes are not classifiable as to their carcinogenicity to humans (Group 3).

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 副作用

Dermatotoxin - 皮肤烧伤。

Dermatotoxin - Skin burns.

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

毒理性

• 毒性数据

大鼠LC50 = 20毫克/立方米/10分钟

LC50 (rat) = 20 mg/m3/10min

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

毒理性

• 相互作用

进行了实验以确定饮食纤维对大鼠T-2毒素中毒的影响。断奶的大鼠被喂以不同水平的纤维素、半纤维素、木质素和果胶，以及含有或不含有T-2毒素（3微克/克饲料）的饲料，持续2周。只有木质素显示出有望克服因喂食T-2毒素而导致的饲料拒绝和生长抑制。进一步的实验表明，喂食苜蓿粉（0%，5%，10%，15%，20%或25%）以及含有或不含有T-2毒素的饲料，这种富含木质素的饲料原料可以很大程度上克服由毒素引起的饲料拒绝和生长抑制。然而，饮食对肝酯酶的活性没有影响，这种酶被认为是分解T-2毒素的酶。大鼠被喂食含有0%，5%，12.5%或20%苜蓿的饲料2周，然后口服给予[(3)H]T-2毒素。饮食中的苜蓿增加了3H的粪便排泄，而尿液排泄不受影响。当口服给予[(3)H]T-2毒素时，苜蓿饲料减少了肾脏和肌肉中的残留(3)H。肠道腔内消化物中的残留(3)H增加了。发现苜蓿饲料减少了肠道转运时间。结论是，苜蓿饲料通过在大肠腔内结合毒素，从而促进粪便排泄，减少了大鼠的T-2毒素中毒。

Experiments were conducted to determine the effect of dietary fibers on T-2 toxicosis in rats. Weanling rats were fed varying levels of cellulose, hemicellulose, lignin and pectin with and without T-2 toxin (3 ug/g feed) for 2 weeks. Only lignin showed promise of overcoming feed refusal and growth depression in animals fed T-2 toxin. Further experiments feeding alfalfa meal (0, 5, 10, 15, 20 or 25%) with and without T-2 toxin indicated that this lignin-rich feedstuff could largely overcome feed refusal and growth depression caused by the toxin. There was no effect of diet, however, on the activity of hepatic esterase, the enzyme believed to catabolize T-2 toxin. Rats were fed diets containing 0, 5, 12.5 or 20% alfalfa for 2 weeks and then dosed orally with [(3)H]T-2 toxin. Dietary alfalfa increased fecal excretion of 3H, whereas urinary excretion was unaffected. Residual (3)H in kidney and muscle was reduced with alfalfa feeding when [(3)H]T-2 toxin was administered orally. Residual (3)H in the digesta in the intestinal lumen increased. Alfalfa feeding was found to reduce intestinal transit time. It was concluded that the feeding of alfalfa reduced T-2 toxicosis in rats by binding the toxin in the intestinal lumen thereby promoting fecal excretion.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

活性氧种被报道可以引起器官损伤。因此，本研究旨在确定氧化应激是否促进了T-2毒素引起的肝脏DNA损伤的起始或进展。研究的目的是还要调查辅酶Q10（CoQ10）和α-生育酚（维生素E）对T-2毒素喂养的小鼠肝脏DNA损伤的行为。对禁食小鼠单次口服灌胃T-2毒素（1.8或2.8 mg/kg体重）处理后，导致76%的肝脏DNA断裂。T-2毒素还显著降低了肝脏谷胱甘肽（GSH）水平。CoQ10（6 mg/kg）与α-生育酚（6 mg/kg）预处理减少了DNA损伤。CoQ10和维生素E对T-2毒素引起的毒性细胞死亡和谷胱甘肽耗竭提供了一些保护。T-2毒素引起的氧化损伤可能是T-2毒素诱导细胞损伤和DNA损伤的潜在机制之一，这最终可能导致肿瘤生成。

Active oxygen species are reported to cause organ damage. This study was therefore designed to determine whether oxidative stress contributed to the initiation or progression of hepatic DNA damage produced by T-2 toxin. The aim of the study was also to investigate the behavior of the antioxidants coenzyme Q10 (CoQ10), and alpha-tocopherol (vitamin E) against DNA damage in the livers of mice fed T-2 toxin. Treatment of fasted mice with a single dose of T-2 toxin (1.8 or 2.8 mg/kg body weight) by oral gavage led to 76% hepatic DNA fragmentation. T-2 toxin also decreased hepatic glutathione (GSH) levels markedly. Pretreatment with CoQ10 (6 mg/kg) together with alpha tocopherol (6 mg/kg) decreased DNA damage. The CoQ10 and vitamin E showed some protection against toxic cell death and glutathione depletion caused by T-2 toxin. Oxidative damage caused by T-2 toxin may be one of the underlying mechanisms for T-2 toxin-induced cell injury and DNA damage, which eventually lead to tumourigenesis.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

T2-三嗪烯能轻易通过猪和鼠的皮肤和肠道被吸收。

T2-Trichothecene is readily absorbed through skin & the gut in pigs & rats.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

T-2毒素会通过哺乳期牛和猪的乳汁传播。

T-2 toxin is transmitted in the milk in lactating cattle & pigs.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

估计每天口服1毫克/千克体重的T-2毒素，连续8天的鸡所产的蛋，相当于饮食中含有的1.6毫克/千克T-2毒素，含有0.9微克此物质。

Estimated that the eggs from chickens treated orally with 1 mg T-2 toxin/kg body weight daily for 8 consecutive days, which is equivalent to 1.6 mg/kg dietary T-2, contain 0.9 ug of this material.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

口服给予小鼠和大鼠(3)H-T2-三线霉素(1 mg/kg体重)后，72小时内通过粪便(55%)和尿液(15%)排出。它分布在肝脏、肾脏和其他器官中，没有特定的积累。

The radioactivity of orally admin (3)H-T2-trichothecene (1 mg/kg body wt) to mice & rats was recovered in feces (55%) & urine (15%) within 72 hr. It was distributed in the liver, kidneys & other organs, without specific accumulation.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

(3)H-T-2毒素通过口服给予小鼠和大鼠后，迅速分布到组织中，并通过粪便和尿液排出。在小鼠口服给药后30分钟，以及在豚鼠肌肉注射后，血浆中的放射性标记物达到最大水平……。在通过饲料给予(3)H-T-2毒素的雏鸡中，血液、血浆、腹部脂肪、心脏、肾脏、肌胃、肝脏和剩余胴体中的最大水平在4小时内达到，而在肌肉、皮肤、胆汁和胆囊中则在12小时内达到……。T-2毒素在猪组织中的分布与鸡类似……。

(3)H-T-2 Toxin given orally to mice and rats was distributed rapidly to tissues and eliminated in feces and urine. Maximal levels of radiolabel were found after 30 min in plasma of mice after oral administration ... and of guinea pigs after intramuscular injection ... . In chicks administered (3)H-T-2 toxin in the diet, maximal levels were reached by 4 hr in blood, plasma, abdominal fat, heart, kidneys, gizzard, liver and the remainder of the carcass and by 12 hr in muscle, skin, bile and gall bladder ... . The distribution of T-2 toxin in tissues of swine was similar to that in chickens ... .

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1(a)
• 危险品标志：
  Xn,T+,F,T
• 安全说明：
  S16,S22,S26,S28,S36,S36/37,S36/37/39,S45
• 危险类别码：
  R20/21/22,R38,R36,R26/27/28,R11
• WGK Germany：
  3
• 海关编码：
  29329990
• 危险品运输编号：
  UN 3462 6.1/PG 1
• 包装等级：
  I
• 危险类别：
  6.1(a)

制备方法与用途

概述

T-2毒素是由镰刀菌产生的A类单端孢霉烯族真菌毒素中毒性最强的一种，对人畜危害较大。它广泛分布于全球各地的玉米和小麦田间作物以及库存谷物中，并在1973年被联合国粮农组织（FAO）和世界卫生组织（WHO）列为天然存在的危险食品污染毒物之一。

性质

T-2毒素是一种四环倍半萜烯化合物，化学名为4β-15-二乙酰氧基-3α-羟基-8α-(3-甲基丁酰氧)-12,13-环氧单端孢霉-9-烯，分子式为C₂₄H₃₄O₉。该毒素性质稳定，在食物生产和加工过程中不易被高压灭菌灭活。需在200～210℃下灭菌30～40分钟或浸泡于NaClO-NaOH溶液中至少4小时才能灭活。一些真菌和酶可以改变并去除T-2毒素的毒性，而环氧环和双键被认为是主要的毒性基团。

生物活性

T-2毒素（T-2 Mycotoxin）是由各种镰刀菌种产生的真菌毒素，在小鼠和大鼠中的半数致死量分别为5.2 mg/kg BWa和1.5 mg/kg BWa。在动物体内，T-2毒素可以转化为多种代谢产物，如HT-2毒素和T-2-triol，这些均为水解产物。

该毒素作为抑制肽基转移酶（60s核糖体亚基）结合及蛋白质合成的抑制剂，在DNA和RNA的合成、磷脂代谢方面干扰，并增加肝脏中脂质过氧化物的水平。此外，它还能在免疫系统、胃肠道组织以及胎儿组织中诱导细胞凋亡。