Phalloidin from Amanita phalloides

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Phalloidin from Amanita phalloides
• 英文别名: (1S,14R,18S,20S,23S,28S,31S,34R)-28-(2,3-dihydroxy-2-methylpropyl)-18-hydroxy-34-[(1S)-1-hydroxyethyl]-23,31-dimethyl-12-thia-10,16,22,25,27,30,33,36-octazapentacyclo[12.11.11.03,11.04,9.016,20]hexatriaconta-3(11),4,6,8-tetraene-15,21,24,26,29,32,35-heptone
• 化学式: C₃₅H₄₈N₈O₁₁S
• 分子量: 788.9
• InChiKey: KPKZJLCSROULON-HPGKBWJOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.7
• 重原子数：
  55
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  317
• 氢给体数：
  11
• 氢受体数：
  12

ADMET

代谢

各种观察表明，绿色蘑菇毒蝇伞的一种有毒成分毒蝇碱本身并不具有毒性，但会在肝脏中进行生物激活。使用3H-去甲基毒蝇碱，一种毒蝇碱的有毒衍生物，得出结论...3H-去甲基毒蝇碱，以及很可能毒蝇碱本身，在大鼠和小鼠的肝脏中未经代谢。在处理过的动物的尿液中发现的次要排泄产物是被3H标记的衍生物的自降解化合物。

VARIOUS OBSERVATIONS SUGGESTED THAT PHALLOIDINE, A POISONOUS CONSTITUENT OF THE GREEN MUSHROOM, AMANITA PHALLOIDES, WOULD NOT BE TOXIC PER SE, BUT WOULD UNDERGO BIOACTIVATION IN THE LIVER. USING (3)H-DEMETHYLPHALLOIN, A TOXIC DERIVATIVE OF PHALLOIDINE, /IT WAS CONCLUDED/...THAT (3)H-DEMETHYLPHALLOIN, AND MOST PROBABLY ALSO PHALLOIDINE, ARE UNMETABOLIZED IN THE LIVERS OF RATS AND MICE. A SECONDARY EXCRETORY PRODUCT IN THE URINE OF TREATED ANIMALS WAS FOUND TO BE AN AUTODEGRADATION COMPOUND OF THE (3)H-LABELED DERIVATIVE.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

利福平预处理（100或300毫克/千克，口服）保护小鼠免受鬼笔菌素（3毫克/千克，腹膜内注射）毒性的影响，表现为死亡率下降。

PRETREATMENT WITH RIFAMPICIN (100 OR 300 MG/KG, ORAL) PROTECTED MICE AGAINST THE TOXICITY OF PHALLOIDIN (3 MG/KG, IP) AS REFLECTED BY THE DECREASE IN THE MORTALITY RATE.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

在老鼠中，由鬼笔鹅膏素诱导的急性肝出血性坏死可以通过用从水飞蓟中提取的植物化合物水飞蓟宾进行治疗来预防。单次剂量的水飞蓟宾预处理完全消除了毒素引起的形态学变化，并显著降低了血清酶的活性。

IN MICE, THE ACUTE HEMORRHAGIC NECROSIS OF THE LIVER INDUCED BY PHALLOIDIN WAS PREVENTED BY TREATMENT WITH SILYBIN, A PLANT COMPOUND ISOLATED FROM SILYBUM MARIANUM. PRETREATMENT WITH A SINGLE DOSE OF SILYBIN COMPLETELY ABOLISHED THE MORPHOLOGIC CHANGES INDUCED BY THE TOXIN, AND SIGNIFICANTLY DECREASED THE ACTIVITIES OF SERUM ENZYMES.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

实验性体外血液灌流，使用活性炭和Amberlite XAD-4离子交换树脂，比血液透析更能增加从肝素化的牛血血浆中消除(14)C标记的鬼笔鹅膏素。

EXPERIMENTAL IN VITRO HEMOPERFUSION WITH ACTIVATED CHARCOAL AND AMBERLITE XAD-4 ION EXCHANGE RESIN INCREASED THE ELIMINATION OF (14)C-LABELED PHALLOIDIN FROM HEPARINIZED CATTLE BLOOD PLASMA MORE THAN HEMODIALYSIS.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

经单独使用螺内酯或联合使用二氢链霉素、硝基呋喃类抗生素和酵母治疗后，由于鬼笔鹅膏素中毒导致的小鼠死亡率降低了30-45%。

THE MORTALITY RATE IN MICE DUE TO POISONING BY PHALLOIDIN WAS DECREASED BY 30-45% AFTER TREATMENT WITH SPIRONOLACTONE ALONE OR AFTER COMBINED TREATMENT WITH DIHYDROSTREPTOMYCIN, NIFUROXAZIDE, AND YEAST.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

显然，像其他稳定化合物一样，二苯并噻吩通过非特异性稳定细胞质膜来发挥其保护作用，可能是通过释放硫自由基。

APPARENTLY DIBENZOTHIOLINE, LIKE OTHER STABILIZING COMPOUNDS, EXERTS ITS PROTECTIVE ACTION BY A NONSPECIFIC STABILIZATION OF THE CELL PLASMA MEMBRANE, PROBABLY BY RELEASE OF THIO RADICALS.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在成年和幼年（17-19天大）大鼠体内和体外，比较了肝素对肝素的摄取、结合和消除。在两个实验组中，肝脏中毒素的浓度与毒性之间没有关系。尽管幼鼠对肝素的耐受性显著高于成年动物，但幼鼠肝脏中的毒素浓度更高，消除速度显著慢于成年大鼠。肝素在肝脏中的高度结合和浓度通过一个非常低的解离常数来解释。

THE UPTAKE, BINDING AND ELIMINATION OF PHALLOIDIN BY LIVER WAS COMPARED IN ADULT AND BABY (17-19 DAYS OLD) RATS IN VIVO AND IN VITRO. IN BOTH GROUPS, THERE WAS NO RELATION BETWEEN THE CONCENTRATION OF THE POISON IN THE LIVER AND THE TOXICITY. ALTHOUGH BABY RATS SHOWED A SIGNIFICANTLY HIGHER TOLERANCE AGAINST PHALLOIDIN THAN THE ADULT ANIMALS, THE CONCENTRATION OF THE POISON IN THE LIVER OF BABY RATS WAS HIGHER, AND THE ELIMINATION WAS SIGNIFICANTLY SLOWER THAN IN ADULT RATS. THE VERY TIGHT BINDING AND CONCENTRATION OF PHALLOIDIN IN THE LIVER WAS EXPLAINED BY AN EXTREMELY LOW DISSOCIATION CONSTANT.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

amanita phalloides 提取物给药后，大鼠尿液中在第一天检测到PHALLOIN和GAMMA-AMANITIN，第二天检测到PHALLOIDIN。

PHALLOIN AND GAMMA-AMANITIN WERE DETECTED WITHIN THE FIRST DAY AND PHALLOIDIN WITHIN THE SECOND DAY IN THE URINE OF RATS AFTER ADMINISTRATION OF AMANITA PHALLOIDES EXTRACTS.

来源:Hazardous Substances Data Bank (HSDB)