(+)-N(4)-{R-[2-(4-methylcyclohex-3-en-1-yl)-propan-2-yl]}thiosemicarbazide | 1175656-95-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (+)-N(4)-{R-[2-(4-methylcyclohex-3-en-1-yl)-propan-2-yl]}thiosemicarbazide
• 英文别名: 1-amino-3-[2-[(1R)-4-methylcyclohex-3-en-1-yl]propan-2-yl]thiourea
• CAS: 1175656-95-7
• 化学式: C₁₁H₂₁N₃S
• 分子量: 227.374
• InChiKey: YIUKHWMWXQSUFM-VIFPVBQESA-N

物化性质

• 熔点：
  125-127 °C
• 沸点：
  327.8±25.0 °C(Predicted)
• 密度：
  1.081±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  82.2
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (+)-N(4)-{R-[2-(4-methylcyclohex-3-en-1-yl)-propan-2-yl]}thiosemicarbazide 、 对甲氧基苯乙酮 在 盐酸 作用下， 以 乙醇 为溶剂， 以88%的产率得到(+)-(R)-N(4)-[2-(4-methylcyclohex-3-en-1-yl)propan-2-yl]-N(1)-[1-(4-methoxyphenyl)ethylidene]thiosemicarbazide
  参考文献：
  名称：

  Novel R-(+)-limonene-based thiosemicarbazones and their antitumor activity against human tumor cell lines

  摘要：

  In an attempt to develop potent and selective antitumor agents, a series of novel thiosemicarbazones derived from a natural monoterpene R-(+)-limonene was synthesized and their antitumor activity was evaluated. Overall, the majority of tested compounds exhibited considerable inhibitory effects on the growth of a wide range of cancer cell lines. Almost all of tested thiosemicarbazones were especially sensitive to prostate cells (PC-3). Derivatives 5, 6, 8, 9, 10, 11 and 13 presented the most potent antitumor activity against PC-3 cells. These compounds showed lower value of GI(50) (0.04-0.05 mu M) than the reference drug paclitaxel, besides a high selectivity for the same cell line. The 4-fluorobenzaldehyde derivative 10 was the most selective compound for prostate cells, while 2-hydroxybenzaldehyde derivative 8 was the most active compound, with potent antitumor activity against all tested cell lines. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.03.086
• 作为产物：
  描述：

  甜橙提取物 在 盐酸 、 potassium hydrogensulfate 、 sodium carbonate 、 肼 作用下， 以 乙醇 、 氯仿 、 水 为溶剂， 反应 27.0h， 生成 (+)-N(4)-{R-[2-(4-methylcyclohex-3-en-1-yl)-propan-2-yl]}thiosemicarbazide
  参考文献：
  名称：

  基于 (-)-莰烯和 R-(+)-柠檬烯的缩氨基硫脲对人黑色素瘤细胞的体外抗增殖和凋亡作用

  摘要：

  评估了一系列 38 种基于莰烯和柠檬烯的缩氨基硫脲衍生物的抗增殖活性。其中，19 种是通过质子和碳 13 核磁共振合成并表征的（ 1手13 13C核磁共振）。对于初始化合物选择，将人黑色素瘤细胞 (SK-MEL-37) 暴露于单一浓度的化合物 (100 μM) 24、48 和 72 小时，并目视观察细胞脱离。使用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑 (MTT) 方法测定细胞活力。 19 种化合物（4、6、8、11、13、14、15、16、17、18、20、22、25、26、31、3'、4'、6' 和 9'）产生的细胞活力如下20%。随后，IC 50处理 72 小时后，确定这些化合物的值范围为 11.56 至 55.38 μM。化合物 17 (o-羟基苯甲醛 (-)-莰烯基缩氨基硫脲）的 IC 值最低50值，然后是 12.84 μM 的化合物 4（基于苯甲醛 (-) 莰烯的缩氨基硫脲）。对于化合物

  DOI：

  10.1371/journal.pone.0295012

文献信息

• Synthesis and comparison of antileishmanial and cytotoxic activities of S-(−)-limonene benzaldehyde thiosemicarbazones with their R-(+)-analogues
  作者：Sabrina A. Almeida Batista、Fábio Vandresen、Hugo Falzirolli、Elizandra Britta、Diogo N. de Oliveira、Rodrigo R. Catharino、Mateus A. Gonçalves、Teodorico C. Ramalho、Felipe A. La Porta、Celso V. Nakamura、Cleuza C. da Silva

  DOI：10.1016/j.molstruc.2018.11.017

  日期：2019.3

  thiosemicarbazones displayed the highest activities, confirming that the monoterpenic moiety is essential for activity. Notably, among the compounds tested, the S-(−)-enantiomer of the 4-nitro-derivative (8d) presented considerably lower cytotoxicity than its R-(+)-analogue, emphasizing the importance of the stereochemistry. The most active derivative (8d) exhibited a potent antiprotozoal activity (IC50 2.4 μM)

  摘要 在这项研究中，我们探索了一系列新的潜在抗原生动物 S-(-)-柠檬烯基苯甲醛缩氨基硫脲的合成，并检查了它们对细胞外前鞭毛体形式的亚马逊利什曼原虫有效的活性。同样，同时，我们的研究小组先前合成的一系列基于 R-(+)-柠檬烯的缩氨基硫脲和缺乏单萜部分的缩氨基硫脲也进行了生物学评估。在这里，我们报告了理论和实验方法的结合以及统计分析，以研究单萜基团及其立体化学对苯甲醛缩氨基硫脲衍生物生物活性的影响，以确定它们的构效关系。萜烯缩氨基硫脲表现出最高的活性，确认单萜部分对于活性是必不可少的。值得注意的是，在测试的化合物中，4-硝基衍生物 (8d) 的 S-(-)-对映异构体的细胞毒性明显低于其 R-(+)-类似物，强调了立体化学的重要性。最活跃的衍生物 (8d) 表现出有效的抗原生动物活性 (IC50 2.4 μM) 和高选择性 (SI > 1147)。此外，在密度泛函理论 (DFT) 水平上进行了理论计算，以表明吉布斯自由能和
• 4-Fluorobenzaldehyde limonene-based thiosemicarbazone induces apoptosis in PC-3 human prostate cancer cells
  作者：Bruna dos Santos Rodrigues、Renato Ivan de Ávila、Polyana Lopes Benfica、Ludmila Pires Bringel、Cecília Maria Alves de Oliveira、Fábio Vandresen、Cleuza Conceição da Silva、Marize Campos Valadares

  DOI：10.1016/j.lfs.2018.04.024

  日期：2018.6

  Aims: This study evaluated parameters of toxicity and antiproliferative effects of (+)-N(1)-4-fluorobenzaldehyde- N(4)-1-methyl-1-[(1R)-4-methylcyclohexene-3-il]-ethyl}-thiossemicarbazone (4-FTSC) in PC-3 adenocarcinoma prostate cells.Main methods: Cytotoxicity of 4-FTSC in PC-3 cells was evaluated using MTT assay. Morphology examination of PC-3 cells treated with 4-FTSC was also performed as well as the cell death mechanisms induced were investigated using flow cytometry. Parameters of toxicity of 4-FTSC was conducted by the investigation of its potential myelotoxicity and lymphotoxicity, hemolytic activity and acute oral toxicity profile.Key findings: 4-FTSC showed promising cytotoxic effects against PC-3 cells (IC50= 18.46 mu M). It also triggered apoptotic morphological changes, phosphatidylserine externalization and a significant increase of DNA fragmentation in PC-3 cells. Moreover, 4-FTSC did not show changes in the PC-3 cell cycle with levels of p21, p27, NF kappa B and cyclin D1 similar to those found in both control and treated cells. 4-FTSC also promoted an increase of p53 levels associated with mitochondrial impairment through loss of Delta Psi m and ROS overproduction. 4-FTSC-induced cell death mechanism in PC-3 cells involved activation of caspase-3/-7 through apoptosis intrinsic pathway via caspase-9. Regarding toxicological profile, 4-FTSC showed in vitro lymphotoxicity, although with low cytotoxicity for bone marrow progenitors and no hemolytic potential. Moreover, it was classified as GHS category 5 (LD50 > 2000-5000 mg/Kg), suggesting it has low acute oral systemic toxicity.Significance: 4-FTSC seems to be a promising candidate to be used as a clinical tool in prostate cancer treatment. Further studies are required to better clarify its toxicopharmacological effects found in this compound.
• Novel R-(+)-limonene-based thiosemicarbazones and their antitumor activity against human tumor cell lines
  作者：Fábio Vandresen、Hugo Falzirolli、Sabrina A. Almeida Batista、Ana Paula B. da Silva-Giardini、Diogo N. de Oliveira、Rodrigo R. Catharino、Ana Lúcia T.G. Ruiz、João E. de Carvalho、Mary Ann Foglio、Cleuza Conceição da Silva

  DOI：10.1016/j.ejmech.2014.03.086

  日期：2014.5

  In an attempt to develop potent and selective antitumor agents, a series of novel thiosemicarbazones derived from a natural monoterpene R-(+)-limonene was synthesized and their antitumor activity was evaluated. Overall, the majority of tested compounds exhibited considerable inhibitory effects on the growth of a wide range of cancer cell lines. Almost all of tested thiosemicarbazones were especially sensitive to prostate cells (PC-3). Derivatives 5, 6, 8, 9, 10, 11 and 13 presented the most potent antitumor activity against PC-3 cells. These compounds showed lower value of GI(50) (0.04-0.05 mu M) than the reference drug paclitaxel, besides a high selectivity for the same cell line. The 4-fluorobenzaldehyde derivative 10 was the most selective compound for prostate cells, while 2-hydroxybenzaldehyde derivative 8 was the most active compound, with potent antitumor activity against all tested cell lines. (C) 2014 Elsevier Masson SAS. All rights reserved.
• In vitro antiproliferative and apoptotic effects of thiosemicarbazones based on (-)-camphene and R-(+)-limonene in human melanoma cells
  作者：Paula Roberta Otaviano Soares、Débora Cristina Souza Passos、Francielly Moreira da Silva、Ana Paula B. da Silva-Giardini、Narcimário Pereira Coelho、Cecília Maria Alves de Oliveira、Lucília Kato、Cleuza Conceição da Silva、Lidia Guillo

  DOI：10.1371/journal.pone.0295012

  日期：——

  proton and carbon-13 nuclear magnetic resonance (1H and 13C NMR). For initial compound selection, human melanoma cells (SK-MEL-37) were exposed to a single concentration of a compound (100 μM) for 24, 48, and 72 hours, and cell detachment was visually observed. Cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Nineteen compounds (4, 6, 8,

  评估了一系列 38 种基于莰烯和柠檬烯的缩氨基硫脲衍生物的抗增殖活性。其中，19 种是通过质子和碳 13 核磁共振合成并表征的（ 1手13 13C核磁共振）。对于初始化合物选择，将人黑色素瘤细胞 (SK-MEL-37) 暴露于单一浓度的化合物 (100 μM) 24、48 和 72 小时，并目视观察细胞脱离。使用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑 (MTT) 方法测定细胞活力。 19 种化合物（4、6、8、11、13、14、15、16、17、18、20、22、25、26、31、3'、4'、6' 和 9'）产生的细胞活力如下20%。随后，IC 50处理 72 小时后，确定这些化合物的值范围为 11.56 至 55.38 μM。化合物 17 (o-羟基苯甲醛 (-)-莰烯基缩氨基硫脲）的 IC 值最低50值，然后是 12.84 μM 的化合物 4（基于苯甲醛 (-) 莰烯的缩氨基硫脲）。对于化合物