[(1R,2R,3E,5S,7S,9E,11R,12S,14S,15R,16S)-16-Benzyl-5,12-dihydroxy-5,7,14-trimethyl-13-methylidene-6,18-dioxo-17-azatricyclo[9.7.0.01,15]octadeca-3,9-dien-2-yl] acetate | 22144-77-0

• 物质功能分类: 天然产物 - 生物碱
• 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: [(1R,2R,3E,5S,7S,9E,11R,12S,14S,15R,16S)-16-Benzyl-5,12-dihydroxy-5,7,14-trimethyl-13-methylidene-6,18-dioxo-17-azatricyclo[9.7.0.01,15]octadeca-3,9-dien-2-yl] acetate
• CAS: 22144-77-0
• 化学式: C₃₀H₃₇NO₆
• 分子量: 507.6
• InChiKey: SDZRWUKZFQQKKV-IBUWGYDRSA-N

物化性质

• 熔点：
  255-260°C
• 沸点：
  595.84°C (rough estimate)
• 密度：
  1.1764 (rough estimate)
• 闪点：
  87℃
• 溶解度：
  可溶于DMSO
• LogP：
  2.640 (est)
• 物理描述：
  Cytochalasin d appears as needles or fluffy white powder. (NTP, 1992)
• 颜色/状态：
  NEEDLES FROM ACETONE-PETROLEUM ETHER
• 旋光度：
  SPECIFIC OPTICAL ROTATION: -7.5 DEG @ 25 °C/D (C= 0.55 IN DIOXANE)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  37
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  113
• 氢给体数：
  3
• 氢受体数：
  6

ADMET

代谢

在工作中使用立体特异性标记的前体，证明了L-苯丙氨酸是细胞松弛素D的主要前体，并且D-和L-对映体通过苯丙酮酸达到快速的平衡，这解释了两种对映体同样有效的掺入。

IN...WORK USING STEREOSPECIFICALLY LABELLED PRECURSORS, L-PHENYLALANINE WAS SHOWN TO BE THE PRIMARY PRECURSOR OF CYTOCHALASIN D, & THE RAPID EQUILIBRIUM OF D- & L-ISOMERS THROUGH PHENYLPYRUVIC ACID WAS SHOWN TO ACCOUNT FOR THE EQUALLY EFFICIENT INCORPORATION OF BOTH ENANTIOMERS.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在粗糙脉孢菌合成素D的生物合成中，[1,2-(13)C]-醋酸盐被加入到这种真菌的生长培养中。完整醋酸单元的排列被确定...素D源自苯丙氨酸、甲硫氨酸和9个完整的醋酸单元。八个醋酸单元以头尾相连的方式结合，形成C16-多酮部分。更高偶数饱和脂肪酸的喂养，如C1标记的丁酸、肉豆蔻酸和棕榈酸，并未显示出直接并入。然而，它们确实经过β-氧化产生C1标记的醋酸，后者被并入素D中。

IN...THE BIOSYNTHESIS OF CYTOCHALASIN D BY ZYGOSPORIUM MASONII, [1,2-(13)C]-ACETATE WAS FED TO A GROWING CULTURE OF THIS FUNGUS. THE ARRANGEMENT OF INTACT ACETATE UNITS WAS ESTABLISHED... CYTOCHALASIN D ORIGINATED FROM PHENYLALANINE, METHIONINE & 9 INTACT ACETATE UNITS. EIGHT OF THE ACETATE UNITS COUPLE IN A HEAD-TO-TAIL FASHION TO FORM THE C16-POLYKETIDE MOIETY. THE FEEDING OF HIGHER EVEN-NUMBERED SATURATED ACIDS SUCH AS C1-LABELLED BUTYRATE, MYRISTATE & PALMITATE SHOWED NO DIRECT INCORPORATION. THEY DO, HOWEVER, UNDERGO BETA-OXIDATION TO YIELD C1-LABELLED ACETATE WHICH IS INCORPORATED INTO CYTOCHALASIN D.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

兔肾细胞用细胞松弛素D预处理增强单纯疱疹病毒2型的感染性3到6倍于使用标准氯化钙技术获得的值。

PRETREATMENT OF RABBIT KIDNEY CELLS WITH CYTOCHALASIN D ENHANCED HERPES SIMPLEX VIRUS TYPE 2 INFECTIVITY 3- TO 6-FOLD OVER VALUES OBTAINED USING THE STANDARD CALCIUM CHLORIDE TECHNIQUE.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

细胞松弛素D处理允许性或半限制性细胞系增强了它们对脊髓灰质炎病毒的感染敏感性。

CYTOCHALASIN D TREATMENT OF PERMISSIVE OR SEMIRESTRICTIVE CELL LINES ENHANCED THEIR SUSCEPTIBILITY TO INFECTION WITH POLIOVIRUS.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

细胞松弛素D对Hela细胞的细胞毒性：样品在DMSO中溶解，浓度为10毫克/毫升，并在培养基中稀释。盖玻片上的细胞进行了为期3天的处理。通过观察染色的盖玻片，估计细胞毒性的程度，范围从'0'（细胞损伤很小）到'4'（完全细胞溶解）。'2'表示大约50%的生长抑制剂量。记录了相应细胞毒性评分的特定剂量：32微克/毫升= 3.5评分；10微克/毫升= 3评分；3.2微克/毫升= 3评分；1.0微克/毫升= 2.5评分；0.32微克/毫升= 1评分。/来自表格/

CYTOTOXICITY OF CYTOCHALASIN D ON HELA CELLS: SAMPLES WERE DISSOLVED IN DMSO AT 10 MG/ML & DILUTED IN THE MEDIUM. CELLS ON COVER-GLASSES WERE TREATED FOR 3-DAYS. DEGREE OF CYTOTOXICITY WAS ESTIMATED ON A SCALE RANGING '0' (LITTLE CELLULAR DAMAGE) THROUGH '4' (COMPLETE CYTOLYSIS) IN OBSERVING THE STAINED COVER-GLASSES. '2' DENOTES APPROXIMATE 50% GROWTH-INHIBITORY DOSE. SPECIFIC DOSAGE WITH RESPECTIVE CYTOTOXICITY RATING WAS NOTED: 32 UG/ML= 3.5 RATING; 10 UG/ML= 3 RATING; 3.2 UG/ML= 3 RATING; 1.0 UG/ML= 2.5 RATING; 0.32 UG/ML= 1 RATING. /FROM TABLE/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

...一份报告描述了细胞松弛素/CYTOCHALASINS/之间的结构-活性关系...ZYGOsporin A（细胞松弛素D）、E、F、G以及30多种衍生物...对HeLa细胞的细胞毒性和皮肤刺激性测试。结果表明，骨架中C(7)位的羟基和C(10)位的苯基对细胞毒性至关重要。

...ONE REPORT HAS DESCRIBED THE STRUCTURE-ACTIVITY RELATIONSHIP AMONG /CYTOCHALASINS/...ZYGOSPORIN A (CYTOCHALASIN D), E, F, G, & MORE THAN 30 DERIVATIVES...FOR CYTOTOXICITY TO HELA CELLS ALONG WITH SKIN IRRITATION TESTS. THE RESULTS INDICATED THAT THE HYDROXYL GROUP AT C(7) & THE PHENYL GROUP AT C(10) IN THE SKELETON ARE ESSENTIAL FOR CYTOTOXICITY.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

细胞松弛素D诱导HeLa和Hep2细胞发生普遍性收缩和皱缩，同时伴随着肌动蛋白、肌球蛋白和原肌球蛋白向细胞中心的转移。

CYTOCHALASIN D INDUCED A GENERALIZED CELL CONTRACTION AND ZEIOSIS IN HELA AND HEP2 CELLS, TOGETHER WITH A CENTRIPETAL TRANSLOCATION OF ACTIN, MYOSIN, AND TROPOMYOSIN.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1(a)
• 危险品标志：
  T
• 安全说明：
  S36,S37,S45
• 危险类别码：
  R25
• WGK Germany：
  2,3
• 海关编码：
  29337900
• 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)

制备方法与用途

生物活性

Cytochalasin D（Zygosporin A；NSC 209835）是一种有效且细胞渗透性的肌动蛋白聚合抑制剂，由真菌产生。它通过与G-actin结合，抑制了G-actin–cofilin的相互作用，并且还能抑制cofilin与F-actin的结合，从而减缓活细胞中肌动蛋白聚合和解聚的速率。Cytochalasin D 可以减少外泌体的释放，进而降低肿瘤环境中survivin的含量。此外，Cytochalasin D 诱导YAP磷酸化，阻止其核易位而保留在胞质中。

靶点

• G-actin