22β-angeloyloxy-3-oxo-olean-12-en-28-oic acid | 67991-51-9

• 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: 22β-angeloyloxy-3-oxo-olean-12-en-28-oic acid
• 英文别名: lantadene X；lantadene A；(4R,4aS,6aR,6aS,6bR,8aR,12aR,14bS)-2,2,6a,6b,9,9,12a-heptamethyl-4-[(E)-2-methylbut-2-enoyl]oxy-10-oxo-3,4,5,6,6a,7,8,8a,11,12,13,14b-dodecahydro-1H-picene-4a-carboxylic acid
• CAS: 67991-51-9
• 化学式: C₃₅H₅₂O₅
• 分子量: 552.795
• InChiKey: KCLIRHUTOPOHKJ-DSYIDUNCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.8
• 重原子数：
  40
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  80.7
• 氢给体数：
  1
• 氢受体数：
  5

ADMET

毒理性

• 相互作用

Lantadenes 是从 Lantana camara L. 叶片中分离出来的五环三萜类化合物，具有抗肿瘤活性。... 当前研究特别设计用于启动这些化合物在化学预防活性中涉及的分子靶点。通过每周两次在剃光的鼠背上涂抹7,12-二甲基苯并(a)蒽 (DMBA) (100 nmol/100 uL 丙酮) 2周，随后涂抹TPA (1.7 nmol/100 uL 丙酮) 20周来诱导皮肤病变。Lantadene A (LA) 和 LA的甲基酯 (LAM) 以50 mg/kg体重的剂量口服给药，每周两次，在DMBA应用前1周开始，并在此后继续给药20周。与仅DMBA/TPA处理的组相比，LA/LAM处理的小鼠病变数量显著减少。通过ELISA观察到，DMBA/TPA处理的小鼠肿瘤中c-jun、p65和p53的蛋白水平显著增加，而在LA和LAM处理的肿瘤中观察到较少的表达。进一步研究了转录因子的免疫组化定位，也显示出与DMBA/TPA处理的肿瘤中的定位相比，LA和LAM处理的肿瘤中c-jun、p65和p53的定位较少。可以推断，LA和LAM的化学预防活性可能与上述分子靶点的调节失调有关...

Lantadenes are pentacyclic triterpenoids isolated from leaves of Lantana camara L. and have antitumor activity. ... The present study was specially designed to initiate the involvement of the molecular targets in chemopreventive activity of these compounds. Skin lesions were induced by twice-weekly topical application of 7,12-dimethylbenz(a)anthracene (DMBA) (100 nmol/100 uL of acetone) for 2 weeks followed by TPA (1.7 nmol/100 uL of acetone) on depilated back of mice for 20 weeks. Lantadene A (LA) and methyl ester of LA (LAM) were administered orally at a dose of 50 mg/kg body weight twice weekly, 1 week before DMBA application and continued for 20 weeks thereafter. A significant decrease in the incidence of number of lesions in mice was obtained in LA/LAM treated groups as compared to DMBA/TPA alone. Significant increase in the protein levels of c-jun, p65, and p53 by ELISA were observed in DMBA/TPA treated mice tumors whereas less expression was observed in LA and LAM treated tumors. Further immunohistochemical localization of transcription factors was studied which also showed less localization of c-jun, p65, and p53 in LA and LAM treated tumors as compared to localization in DMBA/TPA treated tumors. It can be inferred that LA and LAM chemopreventive activity may be linked to the deregulation of above molecular targets ...

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 立即急救：确保已经进行了充分的中毒物清除。如果患者停止呼吸，开始人工呼吸，最好使用需求阀复苏器、袋阀面罩装置或口袋面罩，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。如果发生呕吐，让患者前倾或置于左侧（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受体激动剂，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"，最低流速/。如果出现低血容量的迹象，使用0.9%盐水（NS）或乳酸钠林格氏液。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……。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……。 /Poisons A and 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

• 非人类毒性摘录

实验室动物：急性暴露/兰他定A（22β-当归酰氧基-3-氧代-olean-12-烯-28-酸），来自马缨丹（Lantana camara）叶的五环三萜类化合物，已获得两种多态形式I和II。形式I具有白色、蓬松和棒状的均匀晶体。形式II的颗粒是不规则的、闪亮的和多面的。这两种形式的熔化行为不同。形式I的粉末X射线衍射显示尖锐的峰，而形式II没有明显的峰。从单晶三维X射线结构测定，已经建立了形式I的分子结构。分子的A/B和B/C环是反式融合的，而D/E环是顺式融合的。分子的堆积通过氢键稳定。口服给药时，兰他定A的形式I对豚鼠无毒。形式II引起黄疸和与饲料摄入量和粪便排出量减少、肝肿大、血浆胆红素和酸性磷酸酶活性增加相关的毒性。

/LABORATORY ANIMALS: Acute Exposure/ Lantadene A (22 beta-angeloyloxy-3-oxo-olean-12-en-28-oic acid), a pentacyclic triterpenoid compound from lantana (Lantana camara) leaves has been obtained in two polymorphic forms I and II. Form I had white, fluffy, and rod-shaped uniform crystals. Form II particles were irregular, shining, and polyhedral. The two forms differed in melting behavior. The powder x-ray diffraction of form I showed sharp peaks whereas from II did not contain distinct peaks. From single-crystal three-dimensional x-ray structure determination, the molecular structure of form I has been established. A/B and B/C rings of the molecule are trans fused while D/E rings are cis fused. The packing of the molecule is stabilized by hydrogen bonding. Form I of lantadene A was non-toxic to guinea pigs on oral administration. Form II induced ictericity and toxicity associated with decrease in feed intake and fecal output, hepatomegaly, increase in plasma bilirubin, and acid phosphatase activity.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

豚鼠的肝脏匀浆、胆汁、胆囊、血液、尿液、胃肠道（GIT）内容物和粪便被分析，以检测 Lana 叶中的主要肝毒素，即 Lantadene A（LA）、其同类物和生物转化产物，使用高效液相色谱技术。在肝脏、胆汁、胆囊、血液和尿液中未检测到 Lantadenes。LA 和 Lantadene B（LB）、它们的衍生物还原 Lantadene A（RLA）、还原 Lantadene B（RLB）和两个未识别的代谢物可以在下GIT内容物和粪便中检测到。在体外，将 Lana 叶粉与豚鼠盲肠内容物在无氧条件下孵化，引发了 LA 和 LB 分别向 RLA 和 RLB 的生物转化。另一方面，将 Lana 叶粉与牛瘤胃液在无氧条件下孵化，并未引发 Lantadenes 的生物转化。

/Guinea pig/ liver homogenates, bile, gall bladder, blood, urine, contents of gastrointestinal tract (GIT) and feces were analysed for the principal hepatotoxin in lantana leaves viz. lantadene A (LA), its congeners and biotransformation products, using high performance liquid chromatographic technique. Lantadenes could not be detected in liver, bile, gall bladder, blood and urine samples. LA and lantadene B (LB), their derivatives reduced lantadene A (RLA), reduced lantadene B (RLB) and two unidentified metabolites could be detected in the contents of lower GIT and faeces. In vitro incubation of lantana leaf powder with guinea pig caecal contents under anaerobic conditions elicited biotransformation of LA and LB to RLA and RLB, respectively. On the other hand, incubation of lantana leaf powder with cattle rumen liquor under anaerobic conditions did not elicit biotransformation of lantadenes.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  22β-angeloyloxy-3-oxo-olean-12-en-28-oic acid 在 potassium hydroxide 作用下， 以 乙醇 为溶剂， 反应 6.0h， 生成 22β-hydroxyoleanonic acid
  参考文献：
  名称：

  Synthesis of lantadene analogs with marked in vitro inhibition of lung adenocarcinoma and TNF-α induced nuclear factor-kappa B (NF-κB) activation

  摘要：

  The new series of pentacyclic triterpenoids reduced lantadene A (3), B (4), and 22β-hydroxy-3-oxo-olean-12-en-28-oic acid (5) analogs were synthesized and tested in vitro for their NF-κB and IKKβ inhibitory potencies and cytotoxicity against A549 lung cancer cells. The lead analog (11) showed sub-micromolar activity against TNF-α induced activation of NF-κB and exhibited inhibition of IKKβ in a single-digit micromolar dose. At the same time, 11 showed promising cytotoxicity against A549 lung cancer cells with IC50 of 0.98 μM. The Western blot analysis further showed that the suppression of NF-κB activity by the lead analog 11 was due to the inhibition of IκBα degradation, a natural inhibitor of NF-κB. The physicochemical evaluation demonstrated that the lead analog 11 was stable in the simulated gastric fluid of pH 2, while hydrolyzed at a relatively higher rate in the human blood plasma to release the active parent moieties. Molecular docking analysis showed that 11 was hydrogen bonded with the Arg-31 and Gln-110 residues of the IKKβ.

  DOI：

  10.1016/j.bmcl.2014.06.068
• 作为产物：
  描述：

  岩茨烯A 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 14.0 ℃ 、137.89 kPa 条件下， 反应 5.5h， 生成 lantadene C 、 22β-angeloyloxy-3-oxo-olean-12-en-28-oic acid
  参考文献：
  名称：

  Mahato; Sharma; Pramanik, Journal of the Indian Chemical Society, 1999, vol. 76, # 11-12, p. 723 - 726

  摘要：

  DOI：

文献信息

• Novel lung adenocarcinoma and nuclear factor-kappa B (NF-κB) inhibitors: Synthesis and evaluation of lantadene congeners
  作者：Sharad Kumar Suthar、Hong L. Boon、Manu Sharma

  DOI：10.1016/j.ejmech.2013.12.052

  日期：2014.3

  The C-3, C-17 and C-22 congeners of pentacyclic triterpenoids reduced lantadene A (3), B (4) and 22 beta hydroxyoleanolic acid (5) were synthesized and were tested in vitro for their NF-kappa B and IKK beta inhibitory potencies and cytotoxicity against A549 lung cancer cells. The lead congeners 12 and 13 showed IC50 of 0.56 and 0.42 mu mol, respectively against TNF-alpha. induced activation of NF-kappa B. The congeners 12 and 13 exhibited inhibition of IKK beta in a single-digit micromolar dose and at the same time, 12 and 13 showed marked cytotoxicity against A549 lung cancer cells with IC50 of 0.12 and 0.08 mu mol, respectively. The lead ester congeners were stable in the acidic pH, while hydrolyzed readily in the human blood plasma to release the active parent moieties. (C) 2014 Elsevier Masson SAS. All rights reserved.
• Synthesis of lantadene analogs with marked in vitro inhibition of lung adenocarcinoma and TNF-α induced nuclear factor-kappa B (NF-κB) activation
  作者：Monika、Ankesh Sharma、Sharad Kumar Suthar、Vaibhav Aggarwal、Hong Boon Lee、Manu Sharma

  DOI：10.1016/j.bmcl.2014.06.068

  日期：2014.8

  The new series of pentacyclic triterpenoids reduced lantadene A (3), B (4), and 22β-hydroxy-3-oxo-olean-12-en-28-oic acid (5) analogs were synthesized and tested in vitro for their NF-κB and IKKβ inhibitory potencies and cytotoxicity against A549 lung cancer cells. The lead analog (11) showed sub-micromolar activity against TNF-α induced activation of NF-κB and exhibited inhibition of IKKβ in a single-digit micromolar dose. At the same time, 11 showed promising cytotoxicity against A549 lung cancer cells with IC50 of 0.98 μM. The Western blot analysis further showed that the suppression of NF-κB activity by the lead analog 11 was due to the inhibition of IκBα degradation, a natural inhibitor of NF-κB. The physicochemical evaluation demonstrated that the lead analog 11 was stable in the simulated gastric fluid of pH 2, while hydrolyzed at a relatively higher rate in the human blood plasma to release the active parent moieties. Molecular docking analysis showed that 11 was hydrogen bonded with the Arg-31 and Gln-110 residues of the IKKβ.
• Mahato; Sharma; Pramanik, Journal of the Indian Chemical Society, 1999, vol. 76, # 11-12, p. 723 - 726
  作者：Mahato、Sharma、Pramanik、Sharma

  DOI：——

  日期：——