Phomin | 69804-24-6

• 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
• 英文名称: Phomin
• 英文别名: 7β,20β-dihydroxy-16α-methyl-10-phenyl-24-oxa-[14]cytochalasa-6(12),13t,21t-triene-1,23-dione；Cytochalasin B (Phomin)；Cytocholasin B (Phomin)；Cytochalasin B；2H-Oxacyclotetradec[2,3-d]isoindole-2,18(5H)-dione, 16-benzyl-6,7,8,9,10,12a,13,14,15,15a,16,17-dodecahydro-5,13-dihydroxy-9,15-dimethyl-14-methylene-, (E,E)-(5S,9R,12aS,13S,15S,15aS,16S,18aS)-；(4E,12E)-19-benzyl-6,15-dihydroxy-10,17-dimethyl-16-methylidene-2-oxa-20-azatricyclo[12.7.0.01,18]henicosa-4,12-diene-3,21-dione
• CAS: 69804-24-6
• 化学式: C₂₉H₃₇NO₅
• 分子量: 479.616
• InChiKey: GBOGMAARMMDZGR-LFKALUBKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  35
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  95.9
• 氢给体数：
  3
• 氢受体数：
  5

ADMET

毒理性

• 毒性总结

细丝蛋白素是已知能结合到微丝的尖端，快速生长的正端，这会阻止个别肌动蛋白单体从结合端组装和分解。一旦结合，细丝蛋白素基本上就封住了新的肌动蛋白丝的末端。一个细丝蛋白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，细丝蛋白素可以改变细胞形态，抑制诸如细胞分裂等细胞过程，并导致细胞凋亡。细丝蛋白素B还抑制葡萄糖运输和血小板聚集。它阻断了腺苷诱导的凋亡体形成，而不影响白血病HL-60细胞内源性ADP-核糖化的激活。(A2910, A2911, L1913, L1914)

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 B also inhibits glucose transport and platelet aggregation. It blocks adenosine-induced apoptotic body formation without affecting activation of endogenous ADP-ribosylation in leukemia HL-60 cells. (A2910, A2911, L1913, L1914)

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、血小板聚集和血栓收缩、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。细胞松弛素B还会导致细胞内腐胺和精胺水平的逐渐但显著下降。

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. Cytochalasin B also causes gradual but marked decline in intracellular levels of putrescine and spermidine. (A2908, L1916)

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）。 (A3101)

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

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 毒性数据

LD50：11毫克/千克（大鼠腹膜内注射）(L1915)

LD50: 11 mg/kg (Intraperitoneal, Rat) (L1915)

来源:Toxin and Toxin Target Database (T3DB)

反应信息

• 作为反应物：
  描述：

  Phomin 在 chromium(VI) oxide 、 manganese(IV) oxide 作用下， 以 氯仿 、 丙酮 为溶剂， 生成 16α-methyl-10-phenyl-24-oxa-[14]cytochalasa-6(12),13t,21t-triene-1,7,20,23-tetraone
  参考文献：
  名称：

  细胞松弛素A和B的结构

  摘要：

  已经确定了细胞松弛素A和B的结构，即蠕形孢霉的代谢产物对哺乳动物细胞显示出新的作用。细胞松弛素B与光合作用相同。（-）-α-甲基己二酸显示具有R-构型，与先前的分配相反；因此，需要对Nupheus生物碱的绝对构型进行修订。

  DOI：

  10.1039/j39670001667

文献信息

• The absolute stereochemistry of phomin: X-ray analysis of the phomin–silver fluoroborate complex
  作者：G. M. McLaughlin、G. A. Sim、J. R. Kiechel、Ch. Tamm

  DOI：10.1039/c29700001398

  日期：——

  The absolute stereochemistry of the macrolide antibiotic phomin has been determined by X-ray analysis of the phomin–silver fluoroborate complex and chemical correlation with (+)-3-methylpimelic acid.

  的大环内酯抗生素phomin的绝对立体化学已经被确定X 3-methylpimelic酸-与（+）的phomin银，氟硼酸络合物和化学相关的射线分析。
• Gmelin Handbuch der Anorganischen Chemie, Gmelin Handbook: Ag: MVol.B6, 1.5.1.3, page 70 - 71
  作者：

  DOI：——

  日期：——
• BOTTALICO, ANTONIO;CAPASSO, RENATO;EVIDENTE, ANTONIO;RANDAZZO, GIACAMINO;+, PHYTOCHEMISTRY, 29,(1990) N, C. 93-96
  作者：BOTTALICO, ANTONIO、CAPASSO, RENATO、EVIDENTE, ANTONIO、RANDAZZO, GIACAMINO、+

  DOI：——

  日期：——
• The structures of cytochalasins A and B
  作者：D. C. Aldridge、J. J. Armstrong、R. N. Speake、W. B. Turner

  DOI：10.1039/j39670001667

  日期：——

  The structures of cytochalasins A and B, metabolites of Helminthosporium dematioideum showing novel effects on mammalian cells, have been determined. Cytochalasin B is identical with phomin. (–)-α-Methyladipic acid is shown to have the R-configuration contrary to a previous assignment; the absolute configurations of the Nupheus alkaloids therefore require revision.

  已经确定了细胞松弛素A和B的结构，即蠕形孢霉的代谢产物对哺乳动物细胞显示出新的作用。细胞松弛素B与光合作用相同。（-）-α-甲基己二酸显示具有R-构型，与先前的分配相反；因此，需要对Nupheus生物碱的绝对构型进行修订。