来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
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 ...
/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/
/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……。 /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/
/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.
The synthesis of non-steroidal anti-inflammatory drug (NSAID)–lantadene prodrugs as novel lung adenocarcinoma inhibitors via the inhibition of cyclooxygenase-2 (COX-2), cyclin D1 and TNF-α-induced NF-κB activation
作者：Sharad Kumar Suthar、Hong Boon Lee、Manu Sharma
DOI：10.1039/c4ra00280f
日期：——
The ester conjugates of potent nuclear factor-kappa B (NF-κB) inhibitors with cyclooxygenase (COX) inhibiting non-steroidal anti-inflammatory drugs (NSAIDs) present a novel approach towards cancer treatment. The ester prodrugs of pentacyclic triterpenoid 3β,22β-dihydroxy-olean-12-en-28-oic acid (4) with different NSAIDs were synthesized for the dual inhibition of NF-κB and COX-2. The results indicated that the lead compound 14 suppressed the tumor necrosis factor-alpha-induced (TNF-α-induced) activation of NF-κB by inhibiting the inhibitor of the nuclear factor-kappa B kinase (IKK) activation, the inhibitor of the nuclear factor-kappa B alpha (IκBα) degradation and at the same time, it down-regulated the NF-κB mediated protein expression of COX-2 and cyclin D1. Furthermore, compound 14 inhibited lung adenocarcinoma A549 cell proliferation in a dose dependent manner and was found to be 50 folds more active than cisplatin in terms of IC50. Compound 14 was also found to be stable in an acidic pH, while it hydrolyzed readily in human plasma to release the active promoieties. From the results it can be inferred that the lantadeneâNSAID prodrugs are promising anticancer candidates against lung cancer with a dual inhibition capability against both NF-κB and COX-2.
强效核因子-kappa B（NF-κB）抑制剂与环氧合酶（COX）抑制性非甾体抗炎药物（NSAIDs）的酯共轭物为癌症治疗提供了一种新颖的方法。合成了不同的NSAIDs与五环三萜类化合物3β，22β-二羟基-油烯-12-烯-28-酸（4）的酯前药，以实现对NF-κB和COX-2的双重抑制。结果表明，主要化合物14通过抑制核因子-kappa B激酶（IKK）的激活，抑制核因子-kappa B alpha（IκBα）的降解，并同时下调NF-κB介导的COX-2和细胞周期蛋白D1的蛋白表达，抑制了肿瘤坏死因子-alpha诱导的（TNF-α诱导的）NF-κB激活。此外，化合物14以剂量依赖的方式抑制肺腺癌A549细胞的增殖，并且其IC50值比顺铂高50倍。化合物14在酸性pH下稳定，而在人体血浆中则容易水解释放活性前体。从结果可以推断，lantadene-NSAID前药具有抑制NF-κB和COX-2的双重能力，有望成为针对肺癌的有前景的抗癌候选药物。
Exploration of anticancer potential of Lantadenes from weed Lantana camara: Synthesis, in silico, in vitro and in vivo studies
Naturally occurring pentacyclic triterpenoids and their semisyntheticanalogues have engrossed increasing attention for their anticancer potential and exhibiting promising role in discovery of new anticancer agents. Present study include the semi synthetic modifications of Lantadenes from the weed Lantana carama and their structures delineation by FT-IR, 1H-NMR, 13C-NMR & mass spectroscopy. All the
Synthesis and in vitro anticancer studies of novel C-2 arylidene congeners of lantadenes
作者：Navin K. Tailor、Hong L. Boon、Manu Sharma
DOI：10.1016/j.ejmech.2013.04.009
日期：2013.6
The antitumor pentacyclic triterpenoids, Lantadene A (1) and B (2) were isolated from the leaves of weed Lantana camara L. (Verbenaceae) and were structurally transformed to bioactive intermediates 3-6. The Claisen-Schmidt reaction of 22 beta-hydroxy-3-oxoolean-12-en-28-oic acid (5) with requisite aldehydes afforded 2-arylidene-22 beta-hydroxy-3-oxoolean-12-en-28-oic acids (7-16). The compounds were evaluated for their in-vitro anticancer activity by National Cancer Institute (NCI), USA and some of these compounds showed marked cytotoxicity in micromolar range. The mean graph midpoint (MG_MID) value of compound 3 (MG_MID -5.69) was higher than standard drug cisplatin (MG_MID -5.66) while comparable in case of compound 12 (MG_MID -5.52). The NCI's COMPARE molecular mechanistic analysis showed that these compounds were in significant correlations with activity patterns of mechanistic set of compounds (PCC >= 0.60). (C) 2013 Elsevier Masson SAS. All rights reserved.
Barton et al., Journal of the Chemical Society, 1954, p. 903,906
作者：Barton et al.
DOI：——
日期：——
Barton et al., Journal of the Chemical Society, 1954, p. 3689,3691
