3-O-acetylurs-12-en-28-n-butyl ester

• 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: 3-O-acetylurs-12-en-28-n-butyl ester
• 英文别名: 3β-acetoxy-urs-12-en-28-oic acid n-butyl ester；3β-acetoxy-ursen-(12)-oic acid-(28)-butyl ester；3β-Acetoxy-ursen-(12)-saeure-(28)-butylester；butyl (1S,2R,4aS,6aR,6aS,6bR,8aR,10S,12aR,14bS)-10-acetyloxy-1,2,6a,6b,9,9,12a-heptamethyl-2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picene-4a-carboxylate
• 化学式: C₃₆H₅₈O₄
• 分子量: 554.854
• InChiKey: QKEWTSFKGDKJPI-PNOHBZKLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.5
• 重原子数：
  40
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  熊果酸 在 吡啶 、 4-二甲氨基吡啶 、 草酰氯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 3-O-acetylurs-12-en-28-n-butyl ester
  参考文献：
  名称：

  Drug Resistance Reversal Potential of Ursolic Acid Derivatives against Nalidixic Acid- and Multidrug-resistantEscherichia coli

  摘要：

  As a part of our drug discovery program, ursolic acid was chemically transformed into six semi‐synthetic derivatives, which were evaluated for their antibacterial and drug resistance reversal potential in combination with conventional antibiotic nalidixic acid against the nalidixic acid‐sensitive and nalidixic acid‐resistant strains of Escherichia coli. Although ursolic acid and its all semi‐synthetic derivatives did not show antibacterial activity of their own, but in combination, they significantly reduced the minimum inhibitory concentration of nalidixic acid up to eightfold. The 3‐O‐acetyl‐urs‐12‐en‐28‐isopropyl ester (UA‐4) and 3‐O‐acetyl‐urs‐12‐en‐28‐n‐butyl ester (UA‐5) derivatives of ursolic acid reduced the minimum inhibitory concentration of nalidixic acid by eightfold against nalidixic acid‐resistant and four and eightfold against nalidixic acid‐sensitive, respectively. The UA‐4 and UA‐5 were further evaluated for their synergy potential with another antibiotic tetracycline against the multidrug‐resistant clinical isolate of Escherichia coli‐KG4. The results showed that both these derivatives in combination with tetracycline reduced the cell viability in concentration‐dependent manner by significantly inhibiting efflux pump. This was further supported by the in silico binding affinity of UA‐4 and UA‐5 with efflux pump proteins. These ursolic acid derivatives may find their potential use as synergistic agents in the treatment of multidrug‐resistant Gram‐negative infections.

  DOI：

  10.1111/cbdd.12491

文献信息

• In vitro and in vivo anticancer activity evaluation of ursolic acid derivatives
  作者：Jing-Wei Shao、Yong-Chao Dai、Jin-Ping Xue、Ji-Chuang Wang、Feng-Ping Lin、Yang-Hao Guo

  DOI：10.1016/j.ejmech.2011.03.050

  日期：2011.7

  Twenty-three ursolic acid (1) derivatives 2-24 (ten novel compounds 8-10, 14-17 and 22-24) modified at the C-3 and the C-28 positions were synthesized, and their structures were confirmed by IR, (1)H NMR, MS, and elemental analysis. The single crystals of compounds 15 and 17 were obtained. The cytotoxic activity of the derivatives was evaluated against HepG2, BGC-823, SH-SY5Y, HeLa and HELF cells by the MTT assay. The induction of apoptosis and affects on the cell cycle distribution with compound 14 were assessed by fluorescence microscopy, flow cytometry and the activity of caspase-3 in HepG2 cells. Compounds 14-17 had more significant antiproliferative ability against the four cancer cell lines and low cytotoxicity to human embryonic lung fibroblast cells (HELF). Compounds 11, 14-16, 21 and 23 were particularly active against HepG2 cell growth. Compound 14 was selected to investigate cell apoptosis and cell cycle distribution. Flow cytometric analysis and morphologic changes of the cell exhibited that treatment of HepG2 cells with compound 14 led to cell apoptosis accompanied by cell cycle arrest at the S phase in a dose-dependent manner. Furthermore, the activity of the caspase-3 enzyme was increased in the treated cells. In vivo studies using H22 xenografts in Kunming mice were conducted with compound 14 at doses of 50, 100 and 150 mg/kg body weight The results revealed that the medium dosage group (100 mg/kg) showed significant anticancer activity (45.6 +/- 4.3%) compared to the control group. (C) 2011 Elsevier Masson SAS. All rights reserved.
• Sevoflurane mask anesthesia for urgent tracheostomy in an uncooperative trauma patient with a difficult airway
  作者：charles E. Smith、William F. Fallon

  DOI：10.1007/bf03018920

  日期：2000.3

  Purpose: Proper care of the trauma patient often includes tracheal intubation to insure adequate ventilation and oxygenation, protect the airway from aspiration, and facilitate surgery. Airway management can be particularly complex when there are facial bone fractures, head injury and cervical spine instability.Clinical Features: A 29-yr-old intoxicated woman suffered a motor vehicle accident. Injuries consisted of multiple abrasions to her head, forehead, and face, right temporal lobe hemorrhage, and complex mandibular fractures with displacement. Mouth opening was < 10 mm. Blood pressure was 106/71 mmHg, pulse 109, respirations 18, temperature 37.3 degrees C, SpO(2) 100%. Chest and pelvic radiographs were normal and the there was increased anterior angulation of C4-C5 on the cervical spine film. Drug screen was positive for cocaine and alcohol. The initial plan was to perform awake tracheostomy with local anesthesia, However, the patient was uncooperative despite sedation and infiltration of local anesthesia. Sevoflurane, 1%, inspired in oxygen 100%, was administered via face mask. The concentration of sevoflurane was gradually increased to 4%, and loss of consciousness occurred within one minute. The patient breathed spontaneously and required gentle chin lift and jaw thrust. A cuffed tracheostomy tube was surgically inserted without complication. Blood gas showed pH 7.40, PCO2 35 mmHg, PO2 396 mmHg, hematocrit 33.6%. Diagnostic peritoneal lavage was negative. Pulmonary aspiration did not occur. Oxygenation and ventilation were maintained throughout the procedure.Conclusion: Continuous mask Ventilation with sevoflurane is an appropriate technique when confronted with an uncooperative trauma patient with a difficult airway.
• Drug Resistance Reversal Potential of Ursolic Acid Derivatives against Nalidixic Acid- and Multidrug-resistant<i>Escherichia coli</i>
  作者：Gaurav Raj Dwivedi、Anupam Maurya、Dharmendra Kumar Yadav、Feroz Khan、Mahendra P. Darokar、Santosh Kumar Srivastava

  DOI：10.1111/cbdd.12491

  日期：2015.9

  As a part of our drug discovery program, ursolic acid was chemically transformed into six semi‐synthetic derivatives, which were evaluated for their antibacterial and drug resistance reversal potential in combination with conventional antibiotic nalidixic acid against the nalidixic acid‐sensitive and nalidixic acid‐resistant strains of Escherichia coli. Although ursolic acid and its all semi‐synthetic derivatives did not show antibacterial activity of their own, but in combination, they significantly reduced the minimum inhibitory concentration of nalidixic acid up to eightfold. The 3‐O‐acetyl‐urs‐12‐en‐28‐isopropyl ester (UA‐4) and 3‐O‐acetyl‐urs‐12‐en‐28‐n‐butyl ester (UA‐5) derivatives of ursolic acid reduced the minimum inhibitory concentration of nalidixic acid by eightfold against nalidixic acid‐resistant and four and eightfold against nalidixic acid‐sensitive, respectively. The UA‐4 and UA‐5 were further evaluated for their synergy potential with another antibiotic tetracycline against the multidrug‐resistant clinical isolate of Escherichia coli‐KG4. The results showed that both these derivatives in combination with tetracycline reduced the cell viability in concentration‐dependent manner by significantly inhibiting efflux pump. This was further supported by the in silico binding affinity of UA‐4 and UA‐5 with efflux pump proteins. These ursolic acid derivatives may find their potential use as synergistic agents in the treatment of multidrug‐resistant Gram‐negative infections.