(+)-N⁴,N⁴-diethyl-N¹-(6-chloro-2-methoxy-acridin-9-yl)-1-methyl-butanediyldiamine; dihydrochloride | 56100-42-6

• 物质功能分类: 原料药 - 抗寄生虫病药 - 抗疟药
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (+)-N⁴,N⁴-diethyl-N¹-(6-chloro-2-methoxy-acridin-9-yl)-1-methyl-butanediyldiamine; dihydrochloride
• 英文别名: (+)-N⁴,N⁴-Diaethyl-N¹-(6-chlor-2-methoxy-acridin-9-yl)-1-methyl-butandiyldiamin; Dihydrochlorid；(4R)-4-N-(6-chloro-2-methoxyacridin-9-yl)-1-N,1-N-diethylpentane-1,4-diamine;hydrochloride
• CAS: 56100-42-6
• 化学式: C₂₃H₃₀ClN₃O*2ClH
• 分子量: 472.886
• InChiKey: UKZANTJXIMWQCH-PKLMIRHRSA-N

物化性质

• 熔点：
  249-251℃ (Decomposition)
• 密度：
  1.2962 (rough estimate)
• 溶解度：
  可溶于DMSO（轻微）、甲醇（轻微、超声处理）、水（轻微）

计算性质

• 辛醇/水分配系数(LogP)：
  6.39
• 重原子数：
  29.0
• 可旋转键数：
  9.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  37.39
• 氢给体数：
  1.0
• 氢受体数：
  4.0

安全信息

• 危险品标志：
  Xn
• 安全说明：
  S36/37/39,S36/S37/S39
• 危险类别码：
  R22,R36/37/38
• WGK Germany：
  3
• 危险品运输编号：
  NONH for all modes of transport
• 危险标志：
  GHS07
• 危险性描述：
  H302
• 危险性防范说明：
  P301 + P312 + P330

制备方法与用途

生物活性

Quinacrine 2HCl是具有多种作用的亲脂性阳离子药物，通常用作抗原生动物剂。Quinacrine是有效的phospholipase A2抑制剂。

靶点

Target	Value
PLA2 ()

体外研究

Quinacrine (5-20 μM; 24 hours) inhibits the growth of SGC-7901 cells.
Quinacrine (7.5 and 15 μM; 24 hours) induces apoptosis in SGC-7901 cells, which is associated with mitochondria-dependent signal pathway and involves p53 upregulation and caspase-3 activation pathway.
Quinacrine (15 μM; 24 hours) treatment significantly increased the levels of proapoptotic proteins, including cytochrome c, Bax, and p53, and decreased the levels of antiapoptotic protein Bcl-2, thus shifting the ratio of Bax/Bcl-2 in favor of apoptosis .

Cell Viability Assay

Cell Line:	SGC-7901 cells
Concentration:	0, 5, 10, 15, and 20 μM
Incubation Time:	24 hours
Result:	Cell viability was inhibited in a dose-dependent manner, and the mean IC 50 value is 16.18 μM.

Apoptosis Analysis

Cell Line:	SGC-7901 cells
Concentration:	7.5 and 15 μM
Incubation Time:	24 hours
Result:	The percentage of apoptotic cells, including the early phase and late phase apoptosis, increased to 26.30%, compared with control group of 3.37%.

Western Blot Analysis

Cell Line:	SGC-7901 cells
Concentration:	15 μM
Incubation Time:	24 hours
Result:	The relative quantity of cytochrome c protein was upregulated, increased from 0.10 to 0.24. The relative quantity of p53 protein was dramatically increased, from 0.06 to 0.19. The Bax/Bcl-2 ratio was dramatically elevated from 1.21 to 2.59.

体内研究

Quinacrine (100 mg/kg three times per week for two consecutive weeks) significantly suppresses circulating blast cells at days 30/31 and increases the median survival time (MST). Quinacrine does not decrease the body weight of treated animals at the tested dose.

Animal Model:	Female SCID mice with acute myeloid leukemia (AML)-PS model
Dosage:	100 mg/kg
Administration:	Administered by oral gavage (po); three times a week for two consecutive weeks
Result:	In the first AML mouse in vivo study, evaluation of circulating leukemic cells detected in blood samples (in percent of white blood cells (WBC)) at day 30/31 showed 72% human tumor cells in the control mice, whereas in mice treated with Quinacrine, this was only 2.2%. The MST of control mice was 34 days whereas it was 46 days in Quinacrine-treated mice.

类别

有毒物质

毒性分级

中毒

急性毒性

口服- 大鼠 LD50: 660 毫克/ 公斤; 口服- 小鼠 LD50: 557 毫克/ 公斤

可燃性危险特性

可燃;火场释放有毒氮氧化物, 氯化物烟雾

储运特性

库房低温, 通风, 干燥

灭火剂

水, 二氧化碳, 泡沫, 沙土