(2E,4E)-5-(7-acetyloxy-4-methoxycarbonyl-9-methyl-11-oxo-10-oxatricyclo[6.3.2.01,7]tridec-3-en-9-yl)-2-methylpenta-2,4-dienoic acid | 82508-31-4

• 物质功能分类: 生物化工 - 提取物
• 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: (2E,4E)-5-(7-acetyloxy-4-methoxycarbonyl-9-methyl-11-oxo-10-oxatricyclo[6.3.2.01,7]tridec-3-en-9-yl)-2-methylpenta-2,4-dienoic acid
• CAS: 82508-31-4
• 化学式: C₂₃H₂₈O₈
• 分子量: 432.5
• InChiKey: VDGOFNMYZYBUDT-ILBXLQINSA-N

物化性质

• 熔点：
  166°C
• 沸点：
  466.14°C (rough estimate)
• 密度：
  1.2108 (rough estimate)
• 溶解度：
  在甲醇中可溶1mg/mL，透明，无色
• 颜色/状态：
  White to off-white powder or crystals
• 蒸汽压力：
  2.0X10-11 mm Hg at 25 °C (est)
• 解离常数：
  pKa = 4.14 (est)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  116
• 氢给体数：
  1
• 氢受体数：
  8

ADMET

毒理性

• 解毒与急救

/SRP:/ 立即急救：确保已经进行了充分的中和。如果患者停止呼吸，请开始人工呼吸，最好使用需求阀复苏器、球囊阀面罩设备或口袋面罩，按训练操作。如有必要，执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果患者呕吐，让患者向前倾或将其置于左侧（如果可能的话，头部向下），以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗帮助。 /毒物A和B/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立专利气道（如有需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。观察呼吸不足的迹象，如有需要，辅助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，如有必要，进行治疗……。监测休克，如有必要，进行治疗……。预防癫痫发作，如有必要，进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在运输过程中，用0.9%的生理盐水（NS）持续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能吞咽、有强烈的干呕反射且不流口水，则用温水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒药A和B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 高级治疗：对于无意识、严重肺水肿或严重呼吸困难的病人，考虑进行口咽或鼻咽气管插管以控制气道。使用气囊面罩装置的正压通气技术可能有益。考虑使用药物治疗肺水肿……。对于严重的支气管痉挛，考虑给予β激动剂，如沙丁胺醇……。监测心率和必要时治疗心律失常……。开始静脉输注D5W /SRP: "保持开放"，最低流量/。如果出现低血容量的迹象，使用0.9%生理盐水（NS）或乳酸林格氏液。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象……。使用地西泮或劳拉西泮治疗癫痫……。使用丙美卡因氢氯化物协助眼部冲洗……。 /毒物A和B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

/替代和体外测试/ 伪麻酸B（PAB），是从金松科植物Pseudolarix kaempferi Gordon树的根皮中提取出的天然二萜类化合物，具有强大的抗真菌和终止妊娠效果，这可能与血管生成紧密相关。本研究旨在检查其对血管生成的抑制作用，对肿瘤细胞分泌血管内皮生长因子（VEGF）的影响以及可能的作用机制。通过人脐静脉内皮细胞增殖、迁移和管形成实验以及绒毛膜尿囊膜实验来评估血管生成抑制作用。采用ELISA、逆转录PCR和Western印迹分析来检查VEGF蛋白分泌、mRNA表达以及在缺氧MDA-MB-468细胞中可能的作用机制。PAB显示出强大的体外抗血管生成活性，通过以浓度依赖性方式抑制人脐静脉内皮细胞的VEGF刺激增殖和迁移以及胎牛血清刺激的管形成。此外，PAB（每枚10纳米摩尔）在绒毛膜尿囊膜实验中显著抑制了体内血管生成。另一方面，PAB通过减少HIF-1alpha蛋白，消除了MDA-MB-468细胞中由缺氧诱导的VEGF分泌。使用LY294002和U0126的进一步分析表明，缺氧诱导因子1（HIF-1）alpha蛋白水平的增加在缺氧MDA-MB-468细胞中高度依赖于磷脂酰肌醇3'-激酶和p42/p44丝裂原活化蛋白激酶活性。然而，PAB处理并未影响Akt和Erk的活性（磷酸化）形式。有趣的是，选择性的蛋白酶体抑制剂MG-132完全逆转了PAB处理的MDA-MB-468细胞中HIF-1alpha蛋白的减少。PAB通过促进其蛋白酶体介导的降解来减少HIF-1alpha蛋白，从而直接抑制内皮细胞并消除肿瘤细胞中的VEGF旁分泌刺激，这具有潜在的临床相关性。

/ALTERNATIVE and IN VITRO TESTS/ Pseudolaric acid B (PAB), the naturally occurring diterpenoid isolated from the root bark of Pseudolarix kaempferi Gordon tree (Pinaceae), possesses potent antifungal and pregnancy-terminating effects that may be tightly associated with angiogenesis. This study was to examine its angiogenic inhibition, impact on vascular endothelial growth factor (VEGF) secretion from tumor cells and the possible mechanism of action. Angiogenesis inhibition was assessed by the human umbilical vascular endothelial cell proliferation, migration, and tube-formation assays, as well as the chorioallantoic membrane assay. ELISA, reverse transcription-PCR, and Western blotting analyses were performed to examine VEGF protein secretion, mRNA expression, and the possible mechanism in hypoxic MDA-MB-468 cells. PAB displayed potent in vitro antiangiogenic activity shown by inhibiting VEGF-stimulated proliferation and migration and fetal bovine serum-stimulated tube formation of human umbilical vascular endothelial cells in a concentration-dependent manner. Moreover, PAB (10 nmol per egg) significantly suppressed in vivo angiogenesis in the chorioallantoic membrane assay. On the other hand, PAB abrogated hypoxia-induced VEGF secretion from MDA-MB-468 cells via reducing HIF-1alpha protein. Additional analyses using LY294002 and U0126 indicated that the increase in hypoxia-inducible factor 1 (HIF-1)alpha protein level was highly dependent on phosphatidylinositol 3'-kinase and p42/p44 mitogen-activated protein kinase activities in hypoxic MDA-MB-468 cells. However, PAB treatment did not affect the active (phosphorylated) forms of Akt and Erk. Interestingly, the selective proteasome inhibitor MG-132 completely reversed the reduction of HIF-1alpha protein in the PAB-treated MDA-MB-468 cells. PAB displays the dual antiangiogenic activities of directly inhibiting endothelial cells and abrogating paracrine stimulation of VEGF from tumor cells due to reducing HIF-1alpha protein by promoting its proteasome-mediated degradation in MDA-MB-468 cells, which has potential clinical relevance.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

本研究旨在探讨伪麻黄酸B（PAB）对人乳腺癌MCF-7细胞的抑制作用。采用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐分析、形态学变化、橘黄橙染色和琼脂糖凝胶电泳来检测凋亡。通过乳酸脱氢酶活性基础的细胞毒性分析计算凋亡和坏死细胞的百分比；通过检测衰老相关（SA）-β-半乳糖苷酶活性来评估衰老；进行碘化丙啶染色的流式细胞仪分析来调查细胞周期的分布，并通过Western印迹分析检查蛋白质表达。在凋亡过程中，半最大抑制浓度IC50在PAB处理36小时和48小时后分别为3.4和1.35微摩尔/升。暴露于PAB的MCF-7细胞显示出凋亡的典型特征，包括形态变化和DNA片段化。用4微摩尔/升PAB处理36小时的MCF-7细胞发生凋亡，但不是坏死。PAB诱导的凋亡与死亡受体途径无关。衰老细胞变得更大更扁平，SA-β-半乳糖苷酶染色呈阳性。PAB诱导明显的有丝分裂停滞，它先于凋亡和衰老。随着PAB处理，p21和p53的表达上调，cyclin B1上调并从细胞质转运到细胞核，并保持稳定水平。PAB诱导MCF-7细胞的有丝分裂停滞，并通过凋亡和衰老抑制增殖。凋亡与死亡受体途径无关。

/ALTERNATIVE and IN VITRO TESTS/ The aim of the present study was to investigate the inhibitory effect of pseudolaric acid B (PAB) on human breast cancer MCF-7 cells. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide analysis, morphological changes, acridine orange staining, and agarose gel electrophoresis were applied to detect apoptosis. The percentage of apoptotic and necrotic cells was calculated by the lactate dehydrogenase activity-based cytotoxicity assay; senescence associated (SA)-beta-galactosidase activity was detected to evaluate senescence; flow cytometric analysis of propidium iodide staining was carried out to investigate the distribution of cell cycle, and the protein expression was examined by Western blot analysis. During apoptosis, the half maximal inhibitory concentration IC(50)was 3.4 and 1.35 umol/L at 36 and 48 hr after PAB treatment, respectively. The MCF-7 cells exposed to PAB showed typical characteristics of apoptosis, including the morphological changes and DNA fragmentation. The MCF-7 cells treated with 4 umol/L PAB for 36 hr underwent apoptosis, but not necrosis. The apoptosis induced by PAB was independent of the death receptor pathway. The senescent cells became larger and flatter, and the SA-beta-galactosidase staining was positive. PAB induced obvious mitotic arrest and it preceded apoptosis and senescence. The expressions of p21 and p53 was upregulated with PAB treatment, and cyclin B1 was upregulated and transported from the cytoplasm to nuclei, and sustained stable levels. PAB induced mitotic arrest in the MCF-7 cells and inhibited proliferation through apoptosis and senescence. The apoptosis was independent of the death receptor pathway.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• WGK Germany：
  3
• 包装等级：
  III
• 危险类别：
  6.1
• 危险性防范说明：
  P281,P301+P310
• 危险品运输编号：
  2811
• 危险性描述：
  H301,H361

制备方法与用途

概述

土荆皮乙酸（Pseudolaric Acid B，简称PAB）是从土荆皮中提取的一种二萜类化合物。现代药理研究证实，PAB 具有多项生物活性，包括抗癌、抗生育、抗血管生成、抗真菌以及激活过氧化物酶增殖物激活受体（PPAR）等作用。

生物活性

Pseudolaric Acid B 是从金钱松根部分离出的一种二萜酸。它具有多种生物活性：不仅能够抑制乙肝病毒 (HBV) 的分泌，还能诱导细胞自噬；此外，Pseudolaric Acid B 对 T 淋巴细胞有免疫抑制作用，并表现出抗癌和抗真菌的特性。

化学性质

土荆皮乙酸是一种白色结晶粉末，可溶于三氯甲烷、丙酮和甲醇。它来源于土荆皮和金钱松。

用途

土荆皮乙酸具有抗菌、抗炎和抗癌的作用，并可用于含量测定、鉴定及药理实验等研究领域。此外，Pseudolaric Acid B 对大鼠、仓鼠、兔及狗有明显的抗生育作用，对白色念珠菌、须发癣菌和球拟酵母菌等真菌也有抑制作用。