α-倒捻子素 | 6147-11-1

• 物质功能分类: 生物化工 - 中草药成分
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 中文名称: α-倒捻子素
• 中文别名: a-倒捻子素；山竺提取物；罗汉果提取物；曼果斯廷；1,3,6-三羟基-7-甲氧基-2,8-双(3-甲基-2-丁烯基)-9H-氧杂蒽-9-酮
• 英文名称: α-mangostin
• 英文别名: alpha-Mangostin；mangostin；1,3,6-trihydroxy-7-methoxy-2,8-bis(3-methyl-2-butenyl)-9H-xanthen-9-one；1,3,6-trihydroxy-7-methoxy-2,8-bis(3-methyl-2-butenyl)-9H-xanthene-9-one；1,3,6-trihydroxy-7-methoxy-2,8-bis(3-methylbut-2-en-1-yl)-9H-xanthen-9-one；1,3,6-trihydroxy-7-methoxy-2,8-bis(3-methylbut-2-enyl)xanthen-9-one
• CAS: 6147-11-1
• 化学式: C₂₄H₂₆O₆
• 分子量: 410.467
• InChiKey: GNRIZKKCNOBBMO-UHFFFAOYSA-N

物化性质

• 熔点：
  180-182°C
• 沸点：
  640.1±55.0 °C(Predicted)
• 密度：
  1.265±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于甲醇：1mg/mL，透明，淡黄色
• 最大波长(λmax)：
  346nm(MeOH)(lit.)
• 物理描述：
  Solid
• 颜色/状态：
  Faint yellow to yellow powder
• 蒸汽压力：
  9.44X10-15 mm Hg at 25 °C (est)
• 稳定性/保质期：

  Stable under normal temperatures and pressures.

• 分解：
  Nitrogen oxides, carbon monoxide, irritating and toxic fumes and gases, carbon dioxide, nitrogen.
• 聚合：
  Has not been reported.
• 解离常数：
  pKa1 = 3.68 (primary carbonyl); pKa2 = 7.69 (secondary carbonyl); pKa3 = 9.06 (tertiary carbonyl) (est)
• 碰撞截面：
  198.8 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  96.2
• 氢给体数：
  3
• 氢受体数：
  6

ADMET

毒理性

• 相互作用

改变的膜完整性和炎症在心血管损伤中扮演关键角色。作者们研究了外源性给予alpha-山竹素对β-肾上腺素能儿茶酚胺诱导的心血管毒性的有益效果，特别关注了膜ATP酶、溶酶体水解酶以及炎症介质肿瘤坏死因子-α（TNF-α）和环氧合酶-2（COX-2）在白化大鼠中的表达。用异丙肾上腺素（150 mg/kg体重，ip）诱导大鼠2天，显著增加了血清和心脏溶酶体水解酶（β-D-葡萄糖苷酶、β-D-半乳糖苷酶、β-D-N-乙酰葡萄糖苷酶、酸性磷酸酶和组织蛋白酶-D）的活性。心脏中的钠、钙水平显著增加，而钾水平降低，同时伴随着膜结合磷酸酶（Na(+)-K(+) ATP酶、Ca(2+) ATP酶和Mg(2+) ATP酶）的异常活性，在给予ISO的大鼠心脏中观察到这些变化。通过Western印迹法评估心脏TNF-α和COX-2的表达。心脏TNF-α和COX-2的表达在ISO中毒的大鼠中显著升高。预先口服给予alpha-山竹素（200mg/kg体重）8天，显著减轻了这些异常，并使水平恢复到接近正常，与ISO中毒组大鼠相比。总之，alpha-山竹素通过有效减轻ISO诱导的氧化应激和细胞损伤，保持了心肌膜完整性，并减少了异常的TNF-α和COX-2表达。细胞正常化的恢复证明了alpha-山竹素的细胞保护作用。

Altered membrane integrity and inflammation play a key role in cardiovascular damage. /The authors/ investigated the salubrious effect of exogenously administered alpha-mangostin against beta-adrenergic cathecolamine-induced cardiovascular toxicity with special reference to membrane ATPases, lysosomal hydrolases and inflammatory mediators TNF-alpha and Cyclooxygenase-2 (COX-2) expressions in albino rats. Induction of rats with isoproterenol (150 mg/kg body wt, ip) for 2 days resulted in a significant increase in the activities of serum and cardiac lysosomal hydrolases (beta-d-glucuronidase, beta-d-galactosidase, beta-d-N-acetylglucosaminidase, acid phosphatase and cathepsin-D). A significant increase in cardiac levels of sodium, calcium with a decrease in the level of potassium paralleled by abnormal activities of membrane-bound phosphatases (Na(+)-K(+) ATPase, Ca(2+) ATPase and Mg(2+) ATPase) were observed in the heart of ISO-administered rats. Cardiac TNF-alpha and COX-2 expressions were assessed by Western blotting. Cardiac TNF-alpha and COX-2 expressions were significantly elevated in ISO-intoxicated rats. Pre-co-treatment with alpha-mangostin (200mg/kg body wt.) orally for 8 days significantly attenuated these abnormalities and restored the levels to near normalcy when compared to ISO intoxicated group of rats. In conclusion, alpha-mangostin preserves the myocardial membrane integrity and extenuates anomalous TNF-alpha and COX-2 expressions by mitigating ISO-induced oxidative stress and cellular damage effectively. Restoration of cellular normalcy accredits the cytoprotective role of alpha-mangostin.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

顺铂（CDDP）是一种化疗药物，会导致与氧化/硝化应激相关的肾毒性。α-芒果亭（α-M）是从山竹中提取的一种具有抗氧化和抗炎特性的氧杂蒽酮。本研究的目的是评估α-M对顺铂诱导的肾毒性的肾保护作用。α-M以每天12.5毫克/千克的剂量给药，连续10天（顺铂注射前7天和注射后3天）。在第7天，大鼠接受单次顺铂注射（7.5毫克/千克，腹腔注射）；3天后处死大鼠。α-M减轻了肾功能障碍、结构损伤、氧化/硝化应激、过氧化氢酶表达下降以及肿瘤坏死因子α和转化生长因子β的mRNA水平升高。总之，α-M对顺铂诱导的肾毒性的肾保护作用与减轻氧化/硝化应激、炎症和纤维化标志物以及保持过氧化氢酶活性有关。

Cisplatin (CDDP) is a chemotherapeutic agent that produces nephrotoxicity associated with oxidative/nitrosative stress. alpha-Mangostin (alpha-M) is a xanthone extracted from mangosteen with antioxidant and anti-inflammatory properties. The purpose of this study was to evaluate the renoprotective effect of alpha-M on the CDDP-induced nephrotoxicity. alpha-M was administered (12.5 mg/kg/day, i.g.) for 10 days (7 days before and 3 days after CDDP injection). On day 7, rats were treated with a single injection of CDDP (7.5 mg/Kg, i.p.); 3 days after the rats were killed. alpha-M attenuated renal dysfunction, structural damage, oxidative/nitrosative stress, decrease in catalase expression and increase in mRNA levels of tumour necrosis factor alpha and transforming growth factor beta. In conclusion the renoprotective effect of alpha-M on CDDP-induced nephrotoxicity was associated with the attenuation in oxidative/nitrosative stress and inflammatory and fibrotic markers and preservation of catalase activity.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

来自 Garcinia mangostana L. 树皮中的 alpha-Mangostin 被发现对耐万古霉素的肠球菌（VRE）和耐甲氧西林的金黄色葡萄球菌（MRSA）具有活性，其最小抑菌浓度（MIC）分别为6.25和6.25至12.5微克/毫升。我们的研究表明，alpha-Mangostin 与庆大霉素（GM）对 VRE 有协同作用，以及 alpha-Mangostin 与盐酸万古霉素（VCM）对 MRSA 有协同作用。进一步的研究显示，alpha-Mangostin 与市售抗生素如氨苄西林和米诺环素之间存在部分协同作用。这些发现表明，单独使用 alpha-Mangostin 或与 GM 联合对抗 VRE，以及与 VCM 联合对抗 MRSA 可能有助于控制 VRE 和 MRSA 感染。

alpha-Mangostin, isolated from the stem bark of Garcinia mangostana L., was found to be active against vancomycin resistant Enterococci (VRE) and methicillin resistant Staphylococcus aureus (MRSA), with minimum inhibitory concentration (MIC) values of 6.25 and 6.25 to 12.5 ug/mL, respectively. Our studies showed synergism between alpha-mangostin and gentamicin (GM) against VRE, and alpha-mangostin and vancomycin hydrochloride (VCM) against MRSA. Further studies showed partial synergism between alpha-mangostin and commercially available antibiotics such as ampicillin and minocycline. These findings suggested that alpha-mangostin alone or in combination with GM against VRE and in combination with VCM against MRSA might be useful in controlling VRE and MRSA infections.

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)

安全信息

• 危险品标志：
  T
• 安全说明：
  S45
• 危险类别码：
  R25
• WGK Germany：
  1,2
• 海关编码：
  2932999099
• 危险品运输编号：
  UN 2811 6.1 / PGIII
• RTECS号：
  ZD6122420
• 危险性防范说明：
  P501,P273,P270,P264,P301+P312+P330
• 危险性描述：
  H302,H413
• 储存条件：
  2-8°C

制备方法与用途

概述

α-倒捻子素是从山竹子中提取的一种氧杂蒽酮类化合物，源于天然山竹子的有效成分。它具有安全无毒及悠久食用历史等特点，为深入研究α-倒捻子素作为药物提供了理论和应用基础。

生物活性

α-倒捻子素（alpha-MangOSa href=https://www.molaid.com/MS_19470 target="_blank">STin）是一种具有广泛生物活性的膳食呫吨酮，包括抗氧化、抗过敏、抗病毒、抗菌、抗炎及抗癌作用。它也是IDH1突变体（如IDH1-R132H）的抑制剂，Ki值为2.85 μM。

靶点

α-倒捻子素对IDH1-R132H表现出选择性抑制效果，但不抑制IDH1。它以竞争性方式抑制α-酮戊二酸（α-KG）与IDH1-R132H的结合，并在IDH1 (+/R132H) MCF10A细胞中促进5-甲基胞嘧啶和组蛋白H3精氨酸三甲基化位点的去甲基化。在用α-倒捻子素处理的细胞中，细胞增殖以剂量依赖性方式显著减少。α-倒捻子素还增加Bax（促凋亡）、裂解 caspase-3、裂解 caspase-9 和裂解-PARP 的水平。

此外，它显著抑制光诱导的视网膜色素上皮细胞退化及200 μM H₂O₂诱导的RPE细胞凋亡。H₂O₂诱导的活性氧（ROS）生成和光诱导的丙二醛（MDA）生成也被α-倒捻子素抑制。

体内研究

α-倒捻子素通过减少p53表达，降低TAA_DMSO治疗后的肝纤维化风险。与单独使用DMSO相比，在用α-倒捻子素处理后，血清中转氨酶（AST和ALT）的水平显著下降。

化学性质

α-倒捻子素是一种白色结晶粉末，可溶于甲醇、乙醇及DMSO等有机溶剂。它来源于藤黄科山竹壳、罗汉果及山竺。

用途

α-倒捻子素具有治疗腹泻、疟疾、抗炎、抗溃疡以及抗白血病和败血症的作用，可用于含量测定/鉴定/药理实验等。其药理活性包括抗氧化、抗炎、抗菌及抗癌作用。