细胞松驰素 E | 36011-19-5

• 物质功能分类: 原料药 - 抗生素类药物 - 其它抗生素类药
• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 细胞松弛素类
• 中文名称: 细胞松驰素 E
• 中文别名: 细胞松弛素；松胞菌素E；细胞松驰素E
• 英文名称: cytochalasin E
• 英文别名: cytochalsin E；(1S,5E,7R,9S,11E,13S,14S,16R,17S,18S,19S)-19-benzyl-7-hydroxy-7,9,16,17-tetramethyl-2,4,15-trioxa-20-azatetracyclo[11.8.0.01,18.014,16]henicosa-5,11-diene-3,8,21-trione
• CAS: 36011-19-5
• 化学式: C₂₈H₃₃NO₇
• 分子量: 495.573
• InChiKey: LAJXCUNOQSHRJO-ZYGJITOWSA-N

物化性质

• 熔点：
  206 °C
• 沸点：
  587.59°C (rough estimate)
• 密度：
  1.2415 (rough estimate)
• 溶解度：
  DMF：11mg/mL； DMF:PBS (pH7.2) (1:30)：0.03 mg/ml； DMSO：10mg/mL；乙醇：2mg/mL
• LogP：
  1.920 (est)
• 颜色/状态：
  CRYSTALS FROM ACETONE-HEXANE
• 稳定性/保质期：
  UNSTABLE IN CHLOROFORM SOLN & UNDER ACIDIC CONDITIONS.
• 旋光度：
  SPECIFIC OPTICAL ROTATION: -25.6 DEG @ 25 °C/D (IN METHANOL); WEAK ABSORPTIONS BETWEEN 240 & 300 NM DUE IN PART TO THE PI BOND TO PI BOND* TRANSITION OF THE MONOSUBSTITUTED AROMATIC RING

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  36
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  7

ADMET

毒理性

• 毒性总结

细胞松弛素已知能够结合到微丝的尖端，快速生长的正端，从而阻止了单体肌动蛋白从结合端组装和分解。一旦结合，细胞松弛素基本上封住了新的肌动蛋白丝的末端。一个细胞松弛素会结合到一个肌动蛋白丝上。通过阻止肌动蛋白的聚合和延伸，细胞松弛素可以改变细胞形态，抑制细胞分裂等细胞过程，并导致细胞凋亡。细胞松弛素E还能抑制血管生成和肿瘤生长。（A2910, A2911, L1913, L1917）

Cytochalasins are known to bind to the barbed, fast growing plus ends of microfilaments, which then blocks both the assembly and disassembly of individual actin monomers from the bound end. Once bound, cytochalasin essentially caps the end of the new actin filament. One cytochalasin will bind to one actin filament. By blocking the polymerization and elongation of actin, cytochalasins can change cellular morphology, inhibit cellular processes such as cell division, and cause cells to undergo apoptosis. Cytochalasin E also inhibits angiogenesis and tumor growth. (A2910, A2911, L1913, L1917)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

对人类不具有致癌性（未被国际癌症研究机构IARC列名）。

No indication of carcinogenicity to humans (not listed by IARC).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

细胞松弛素的主要生物学效应包括抑制细胞质的分裂、可逆性地抑制细胞运动、诱导核挤出、抑制吞噬作用、血小板聚集和血块收缩、葡萄糖运输、甲状腺分泌以及生长激素的释放。一些细胞松弛素已被证明具有发育效应。对细胞松弛素E进行的动物研究显示了充血性退行性变化、肝脏、肾脏、脾脏、胰腺和小肠的坏死、脑水肿、肺出血以及血管壁的损伤。

Major biological effects of cytochalasins include inhibition of the division of cytoplasm, reversible inhibition of cell movement, induction of nuclear extrusion, inhibition of such processes as phagocytosis, platelet aggregation and clot retraction, glucose transport, thyroid secretion, and release of growth hormone. Some cytochalasins have been shown to have developmental effects. Animal studies with cytochalasin E have shown congestive degenerative changes, necrosis of liver, kidney, spleen, pancreas, and small intestine, brain edema, pulmonary hemorrhages, and injury to vascular walls. (L1916, A2912)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

口服、皮肤、吸入和parenteral（被污染的药物）。

Oral, dermal, inhalation, and parenteral (contaminated drugs). (A3101)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性数据

LD50: 2.60毫克/千克（腹膜内给药，大鼠）（A2912） LD50: 9.10毫克/千克（口服，大鼠）（A2912）

LD50: 2.60 mg/kg (Intraperitoneal, Rat) (A2912) LD50: 9.10 mg/kg (Oral, Rat) (A2912)

来源:Toxin and Toxin Target Database (T3DB)

安全信息

• 危险等级：
  6.1(a)
• 危险品标志：
  T+,T
• 安全说明：
  S28,S36/37,S45
• 危险类别码：
  R26/27/28
• WGK Germany：
  3
• 海关编码：
  29349990
• 危险品运输编号：
  UN 1544 6.1/PG 2
• 包装等级：
  I
• 危险类别：
  6.1(a)
• 危险标志：
  GHS06,GHS08
• 危险性描述：
  H300,H310,H330,H361
• 危险性防范说明：
  P260,P264,P280,P284,P301 + P310,P302 + P350

制备方法与用途

生物活性

Cytochalasin E 是一种含有曲霉衍生真菌代谢产物的环氧化物，能够抑制血管生成和肿瘤生长。它也是一种有效的肌动蛋白解聚剂，能结合肌动蛋白丝的倒刺端并覆盖它，从而防止肌动蛋白伸长。

体外研究

Cytochalasin E 在剂量依赖性的方式下显著抑制 A549 细胞的生长，并且能够诱导自噬相关蛋白 (LC3-II) 和 SQSTM1/p62 的上调。

反应信息

• 作为反应物：
  描述：

  细胞松驰素 E 在 吡啶 、 臭氧 作用下， 以 甲醇 为溶剂， 反应 4.0h， 以79%的产率得到(1S,3aS,6R,7S,7aS)-1-benzyl-3a,6-dihydroxy-6,7-dimethyl-3-oxo-2,3,3a,6,7,7a-hexahydro-1H-isoindole-4-carbaldehyde
  参考文献：
  名称：

  通过碎片化和多样化天然产物来构建3D形状的天然产物（如片段库）

  摘要：

  组装了一个由3D形状的天然产物状片段组成的片段库。文库的构建主要通过天然产物降解和天然产物多样化反应进行，并辅以鉴定3D形状的天然产物，例如可从商业渠道获得的片段。此外，在这些研究过程中，发现了针对Massarigenin C和Cychachalasin E的新型重排。获得的片段库具有出色的3D形状和天然产物相似性，在基于片段的药物发现中涵盖了一个新颖的，尚未开发且代表性不足的化学空间（FBDD）。

  DOI：

  10.1016/j.bmc.2016.12.005
• 作为产物：
  描述：

  alkaline earth salt of/the/ methylsulfuric acid 在 PD-medium 作用下， 反应 1440.0h， 生成 细胞松驰素 E
  参考文献：
  名称：

  细胞松弛素E及其分解产物的核磁共振研究。

  摘要：

  借助1H-1H，1H-13C和1H-13C远程化学位移相关光谱图确定了细胞松弛素E（1）的质子和碳13核磁共振信号，以及分解产物的结构（ 2）确定在中性条件下产生的。

  DOI：

  10.1248/cpb.37.2212

文献信息

• Conveniently implantable sustained release drug compositions
  申请人：Wong G. Vernon

  公开号：US20060073182A1

  公开（公告）日：2006-04-06

  This invention provides for biocompatible and biodegradable syringeable liquid, implantable solid, and injectable gel pharmaceutical formulations useful for the treatment of systemic and local disease states.

  本发明提供了生物相容性和可生物降解的可注射液体、可植入固体和可注射凝胶制药配方，用于治疗系统性和局部疾病状态。
• Pharmaceutical dopamine glycoconjugate compositions and methods of their preparation and use
  申请人：christian T. Samuel

  公开号：US20050250739A1

  公开（公告）日：2005-11-10

  Hydrophilic transportable N-linked glycosyl dopaminergic prodrug compounds according to FORMULA V and methods of their use, wherein, Ring 1 comprises an aryl or heteroaryl ring having 4 to 8 carbon atoms, among which atoms are counted “X” and “Y”; each of X and Y is optional; X, when present is either —C(R 1 ) 2 — or —C(R 1 ) 2 —; Y, when present, is either —CH 2 — or —CH 2 —CH 2 —; z, R 5 and R 5′ . are optional, and when present z, R 5 and R 5′ together form a lower alkyl or a substituted lower alkyl moiety; N is part of either an amine or an amide linkage; E is a saccharide which forms a linkage with N through a single bond from a carbon or oxygen atom thereof; R 1 and R 4 are selected form the group consisting of hydrogen, hydroxyl, halogen, halo-lower alkyl, alkoxyl, alkoxyl-lower alkyl, halo-alkoxy, thioamido, amidosulfonyl, alkoxylcarbonyl, carboxamide, aminocarbonyl, and alkylamino-carbonyl; R 2 and R 3 are hydroxyl; R 5 and R 6 , when present, are selected from the group consisting of hydrogen, hydroxyl, alkoxyl, carbonyl, alkoxylcarbonyl, aminocarbonyl, alkylamino-carbonyl and dialkylamino-carbonyl; and, R 6 and R 6′ are selected from the group consisting of hydrogen, hydroxyl, alkoxyl, carboxyl, alkoxylcarbonyl, aminocarbonyl, alkylamino-carbonyl and dialylamino-carbonyl, with the proviso that Ring 1 is capable of binding to any of: a dopaminergic receptor selected from the group consisting of a D1 receptor and a D5 receptor; a DAT transporter; a VMAT transporter; and, with the proviso that E is capable of binding to a GLUT transporter selected from the group consisting of a GLUT1 receptor and a GLUT3 receptor.

  根据FORMULA V，水亲性可运输的N-连接糖基的多巴胺前药化合物及其使用方法，其中，环1包括一个芳基或杂环芳基环，其中含有4至8个碳原子，其中原子被计为“X”和“Y”；X和Y各自是可选的；当存在X时，它是- C（R1）2-或-C（R1）2-；当存在Y时，它是-CH2-或-CH2-CH2-；z，R5和R5'是可选的，当存在z，R5和R5'时，它们共同形成较低的烷基或取代较低的烷基基团；N是氨基或酰胺连接的一部分；E是一个糖类，通过其碳或氧原子之一的单键与N形成连接；R1和R4从选组中选择，包括氢，羟基，卤素，卤代较低烷基，烷氧基，烷氧基较低烷基，卤代烷氧基，硫酰胺基，氨基磺酰基，烷氧羰基，羧酰胺，氨基羰基和烷基氨基羰基；R2和R3是羟基；当存在时，R5和R6从选组中选择，包括氢，羟基，烷氧基，羰基，烷氧基羰基，氨基羰基，烷基氨基羰基和二烷基氨基羰基；而R6和R6'从选组中选择，包括氢，羟基，烷氧基，羧基，烷氧基羰基，氨基羰基，烷基氨基羰基和二烷基氨基羰基，但前提是环1能够与以下任何一个结合：从选组中选择的多巴胺能感受器，包括D1受体和D5受体；DAT转运体；VMAT转运体；前提是E能够与以下从选组中选择的GLUT转运体结合：GLUT1受体和GLUT3受体。
• Novel pharmaceutical agents containing carbohydrate moieties and methods of their preparation and use
  申请人：Christian T. Samuel

  公开号：US20060189547A1

  公开（公告）日：2006-08-24

  Hydrophilic N-linked pharmaceutical compositions, methods of their preparation and use in neuraxial drug delivery comprising a glycosyl CNS acting prodrug compound covalently N-linked with a saccharide through an amide or an amine bond and a formulary consisting of an additive, a stabilizer, a carrier, a binder, a buffer, an excipient, an emollient, a disintegrant, a lubricating agent, an antimicrobial agent or a preservative, with the proviso that the saccharide moiety is not a cyclodextrin or a glucuronide.

  亲水性N-连接药物组合物，其制备方法和在神经轴向药物输送中的使用，包括一种糖基中枢神经系统作用前药化合物，通过酰胺或胺键与糖苷共价连接，并且配方包括添加剂、稳定剂、载体、粘合剂、缓冲剂、赋形剂、润肤剂、破碎剂、润滑剂、抗微生物剂或防腐剂，但前提是糖苷基团不是环糊精或葡萄糖醛酸盐。
• PHARMACEUTICAL DOPAMINE GLYCOCONJUGATE COMPOSITIONS AND METHODS OF THEIR PREPARATION AND USE
  申请人：Christian Samuel T.

  公开号：US20080194802A1

  公开（公告）日：2008-08-14

  Hydrophilic transportable N-linked glycosyl dopaminergic prodrug compounds according to FORMULA V and methods of their use, wherein, Ring 1 comprises an aryl or heteroaryl ring having 4 to 8 carbon atoms, among which atoms are counted “X” and “Y”; each of X and Y is optional; X, when present is either —C(R 1 ) 2 — or —C(R) 2 —; Y, when present, is either —CH 2 — or —CH 2 —CH 2 —; z, R 5 and R 5′ are optional, and when present z, R 5 and R 5′ together form a lower alkyl or a substituted lower alkyl moiety; N is part of either an amine or an amide linkage; E is a saccharide which forms a linkage with N through a single bond from a carbon or oxygen atom thereof; R 1 and R 4 are selected form the group consisting of hydrogen, hydroxyl, halogen, halo-lower alkyl, alkoxyl, alkoxyl-lower alkyl, halo-alkoxy, thioamido, amidosulfonyl, alkoxylcarbonyl, carboxamide, aminocarbonyl, and alkylamino-carbonyl; R 2 and R 3 are hydroxyl; R 5 and R 6 , when present, are selected from the group consisting of hydrogen, hydroxyl, alkoxyl, carbonyl, alkoxylcarbonyl, aminocarbonyl, alkylamino-carbonyl and dialkylamino-carbonyl; and, R 6 and R 6′ are selected from the group consisting of hydrogen, hydroxyl, alkoxyl, carboxyl, alkoxylcarbonyl, aminocarbonyl, alkylamino-carbonyl and dialylamino-carbonyl, with the proviso that Ring 1 is capable of binding to any of: a dopaminergic receptor selected from the group consisting of a D1 receptor and a D5 receptor; a DAT transporter; a VMAT transporter; and, with the proviso that E is capable of binding to a GLUT transporter selected from the group consisting of a GLUT1 receptor and a GLUT3 receptor.

  根据公式V及其使用方法，水亲和性可转运的N-连接糖基多巴胺前药化合物，其中，环1包括4至8个碳原子的芳基或杂芳基环，其中原子计算为“X”和“Y”；X和Y各自是可选的；当存在X时，它是—C（R1）2—或—C（R）2—；当存在Y时，它是—CH2—或—CH2—CH2—；z，R5和R5'是可选的，当存在时，z，R5和R5'共同形成较低的烷基或取代较低的烷基基团；N是胺或酰胺连接的一部分；E是一种糖，通过其碳或氧原子中的单键与N形成连接；R1和R4从氢、羟基、卤素、卤素较低烷基、烷氧基、烷氧基较低烷基、卤素烷氧基、硫酰胺、氨基磺酰、烷氧基羰基、羧酰胺、氨基羰基和烷基氨基羰基中选择；R2和R3是羟基；当存在R5和R6时，它们从氢、羟基、烷氧基、羰基、烷氧基羰基、氨基羰基、烷基氨基羰基和二烷基氨基羰基中选择；R6和R6'从氢、羟基、烷氧基、羧基、烷氧基羰基、氨基羰基、烷基氨基羰基和二烷基氨基羰基中选择，但环1能够与以下任意一种结合：D1受体和D5受体中选择的多巴胺能受体；DAT转运体；VMAT转运体；并且，E能够与GLUT1受体和GLUT3受体中选择的GLUT转运体结合。
• Novel Pharmaceutical Agents Containing Carbohydrate Moieties And Methods Of Their Preparation And Use
  申请人：Christian Samuel T.

  公开号：US20110237544A1

  公开（公告）日：2011-09-29

  Hydrophilic N-linked pharmaceutical compositions, methods of their preparation and use in neuraxial drug delivery comprising a glycosyl CNS acting prodrug compound covalently N-linked with a saccharide through an amide or an amine bond and a formulary consisting of an additive, a stabilizer, a carrier, a binder, a buffer, an excipient, an emollient, a disintegrant, a lubricating agent, an antimicrobial agent or a preservative, with the proviso that the saccharide moiety is not a cyclodextrin or a glucuronide.

  亲水性N-连接的药物组成物、其制备方法和在神经轴药物输送中的使用，包括一种糖基CNS作用的前药化合物，通过酰胺或胺键与糖分子共价连接，并由添加剂、稳定剂、载体、粘合剂、缓冲剂、赋形剂、润肤剂、崩解剂、润滑剂、抗微生物剂或防腐剂组成的制剂，前提是糖分子部分不是环糊精或葡糖醛酸盐。