3-methylbutanoic acid [(2R,6S,7R,8R)-3-[[(3-formamido-2-hydroxyphenyl)-oxomethyl]amino]-8-hexyl-2,6-dimethyl-4,9-dioxo-1,5-dioxonan-7-yl] ester | 1397-94-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-methylbutanoic acid [(2R,6S,7R,8R)-3-[[(3-formamido-2-hydroxyphenyl)-oxomethyl]amino]-8-hexyl-2,6-dimethyl-4,9-dioxo-1,5-dioxonan-7-yl] ester
• 英文别名: [(2R,6S,7R,8R)-3-[(3-formamido-2-hydroxybenzoyl)amino]-8-hexyl-2,6-dimethyl-4,9-dioxo-1,5-dioxonan-7-yl] 3-methylbutanoate
• CAS: 1397-94-0
• 化学式: C₂₈H₄₀N₂O₉
• 分子量: 548.6
• InChiKey: UIFFUZWRFRDZJC-KSVNMYRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  39
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  157
• 氢给体数：
  3
• 氢受体数：
  9

ADMET

毒理性

• 相互作用

抗霉素A在消除氧气消耗的浓度下，对t-丁基过氧化氢在U937细胞中引发的毒性有轻微的抑制作用，尽管这种作用在统计学上是显著的。保护作用在处理后6小时观察到，但在24小时后不再明显。出乎意料的是，这些事件与低浓度t-丁基过氧化氢产生的DNA单链断裂的显著积累有关。实验发现，在t-丁基过氧化氢处理过程中会产生一个以氧为中心的自由基和一个以碳为中心的自由基，而抗霉素A显著降低了它们的形成。因此，抑制复合物III水平的电子传递似乎（a）减少了介导t-丁基过氧化氢致死效应的有毒物种的形成，至少部分是这样，（b）并促进了在低浓度t-丁基过氧化氢时生成的DNA损伤物种的形成。鱼藤酮和氰化物分别抑制复合物I和IV，它们并不影响t-丁基过氧化氢引发的DNA损伤。这些结果表明，DNA单链断裂并不介导t-丁基过氧化氢的毒性，特定的线粒体功能可能调节有机过氧化物产生的有毒物种和DNA损伤物种的形成。

Antimycin A at levels that abolish oxygen consumption had a slight, although statistically significant, inhibitory effect on the toxicity elicited by t-butylhydroperoxide in U937 cells. The protective effect was observed after 6 hr of post-treatment incubation, but was no longer apparent after 24 hr. Unexpectedly, these events were associated with a marked accumulation of DNA single-strand breaks produced by low levels of t-butylhydroperoxide. Both an oxygen- and a carbon-centred radical were found to arise during treatment with t-butylhydroperoxide, and their formation was significantly lowered by antimycin A. Thus inhibition of electron transport at the level of complex III appears (a) to decrease the formation of toxic species which mediate, at least partially, the lethal effects elicited by t-butylhydroperoxide, and (b) to enhance the formation of DNA-damaging species generated at low concentrations of t-butylhydroperoxide. Rotenone and cyanide, which respectively inhibit complexes I and IV, did not affect DNA damage elicited by t-butylhydroperoxide. These results suggest that DNA single-strand breaks do not mediate the toxicity of t-butylhydroperoxide, and that specific mitochondrial functions might modulate the formation of the toxic and of DNA-damaging species generated by organic hydroperoxides.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

基本治疗：建立专利气道。如有必要，进行吸痰。观察呼吸不足的迹象，如有需要，协助通气。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……。预见并处理癫痫发作……。对于眼睛污染，立即用水冲洗眼睛。在运输过程中，用生理盐水连续冲洗每只眼睛……。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/

Basic treatment: Establish a patent airway. 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 normal saline 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 ... . /Poison A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

高级治疗：对于无意识、严重肺水肿或呼吸停止的患者，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。监测心率和必要时治疗心律失常。 ... 开始静脉输液，使用D5W/SRP：“保持开放”，最低流量/。如果出现低血容量的迹象，使用乳酸钠林格氏液。注意液体过载的迹象。考虑使用药物治疗肺水肿。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（安定）治疗癫痫。使用丙美卡因氢氯化物协助眼部冲洗。/毒药A和B/

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

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

/替代体外测试/研究了代谢毒素抗霉素A（4.1微克/毫升）和2-脱氧葡萄糖（32.2毫摩尔）对洗涤人血小板中5-羟色胺（5HT）的摄取和囊泡储存的影响。在加入代谢毒素后的15秒内，H3-5HT开始从囊泡移动到细胞质中。在加入毒素30分钟后，几乎所有血小板的5HT似乎都存在于细胞质中。代谢毒素迅速作用，在加入后1分钟内，从细胞外介质摄取H3-5HT的血浆膜摄取量减少了大约20%。这可能是直接影响，而不是由于细胞质或囊泡中的5HT改变导致的结果，因为具有正常数量10%以下囊泡储存位点的血小板在加入代谢毒素后也表现出类似的减少。

/ALTERNATIVE IN VITRO TESTS/ The effects of the metabolic poisons antimycin A (4.1 mug/mL) and 2-deoxyglucose (32.2 mM) on the uptake and vesicular storage of serotonin (5HT) in washed human platelets were examined. Within 15 s after the addition of the metabolic poisons, H3-5HT began to move from vesicles into the cytoplasm. By 30 min after poison addition, essentially all the platelet 5HT appeared to be cytoplasmic. The metabolic poisons acted rapidly to decrease plasma-membrane uptake of H3-5HT from the extracellular medium by approximately 20% within 1 min after their addition. This may represent a direct effect rather than one resulting from altered cytoplasmic or vesicular 5HT, since platelets with < 10% of the normal number of vesicular storage sites exhibited a similar reduction after addition of the metabolic poisons.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

体外替代测试/研究了鱼藤酮、抗霉素A、氰化钾和2,4-二硝基苯酚对健康男性精液样本中人类精子运动能力的影响。在所使用的浓度下（10^-6至10^-3），这些化合物均未抑制精子运动。

/ALTERNATIVE IN VITRO TESTS/ The effects of rotenone, antimycin A, potassium cyanide and 2,4-dinitrophenol, on human sperm motility, were studied using semen samples from healthy men. None of the /compounds/ inhibited sperm motility at concentrations used (10-6 to 10-3).

来源:Hazardous Substances Data Bank (HSDB)