(R)-4-(2-isothiocyanatopropan-2-yl)-1-methylcyclohex-1-ene

• 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: (R)-4-(2-isothiocyanatopropan-2-yl)-1-methylcyclohex-1-ene
• 英文别名: (4R)-4-(2-isothiocyanatopropan-2-yl)-1-methylcyclohexene
• 化学式: C₁₁H₁₇NS
• 分子量: 195.329
• InChiKey: PYTUZXYMIOQNAP-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  13
• 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：
  44.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (R)-4-(2-isothiocyanatopropan-2-yl)-1-methylcyclohex-1-ene 在 盐酸 、 sodium carbonate 、 肼 作用下， 以 乙醇 、 水 为溶剂， 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
• 作为产物：
  描述：

  甜橙提取物 、 potassium thioacyanate 在 potassium hydrogensulfate 作用下， 以 氯仿 为溶剂， 反应 24.0h， 生成 (R)-4-(2-isothiocyanatopropan-2-yl)-1-methylcyclohex-1-ene
  参考文献：
  名称：

  S-(-)-柠檬烯苯甲醛缩氨基硫脲及其 R-(+)-类似物的抗利什曼原虫和细胞毒活性的合成和比较

  摘要：

  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

  DOI：

  10.1016/j.molstruc.2018.11.017

文献信息

• A direct route to terpene isothiocyanates
  作者：C.C. da Silva、V. Almagro、A.J. Marsaioli

  DOI：10.1016/s0040-4039(00)61683-0

  日期：1993.10

  An expedient entry into the preparation of isothiocyanate terpenes is presented. The method involves the addition of isothiocyanic acid prepared “in situ” to terminal double bonds.

  提出了方便地制备异硫氰酸酯萜烯的方法。该方法包括将“原位”制备的异硫氰酸加到末端双键上。
• Antiproliferative Activity and Ultrastructural Changes in Promastigote and Amastigote forms of <i>Leishmania amazonensis</i> Caused by Limonene‐Acylthiosemicarbazide Hybrids
  作者：Alex Graça Contato、Vanessa Kaplum、Débora Botura Scariot、Francielle Pelegrin Garcia、Hugo Falzirolli、Fábio Vandresen、Tânia Ueda‐Nakamura、Sueli de Oliveira Silva、Cleuza Conceição da Silva、Celso Vataru Nakamura

  DOI：10.1002/cbdv.202300523

  日期：2023.7

  annually. During the life cycle, the Leishmania parasite alternates between promastigote and amastigote forms. The first line treatment for leishmaniasis are the pentavalent antimonials, such as N-methylglucamine antimoniate (Glucantime®) and sodium stibogluconate (Pentostam®). These drugs are commonly related to be associated with dangerous side effects such as cardiotoxicity, nephrotoxicity, hepatotoxicity

  利什曼病是一种热带人畜共患病。它存在于 98 个国家，估计每年有 130 万人受到影响。在生命周期中，利什曼原虫寄生虫在前鞭毛体和无鞭毛体形式之间交替。利什曼病的一线治疗方法是五价锑剂，例如 N-甲基葡萄糖胺锑酸盐 (Glucantime®) 和葡萄糖酸锑钠 (Pentostam®)。这些药物通常与危险的副作用有关，例如心脏毒性、肾毒性、肝毒性和胰腺炎。考虑到这些方面，这项工作旨在获得一系列新的柠檬烯-酰基氨基硫脲杂合体作为治疗利什曼病的替代方案。为此，在抗增殖测定中使用了亚马逊利什曼原虫的前鞭毛体、纯无鞭毛体和细胞内无鞭毛体；J774-A1巨噬细胞用于细胞毒性测定；采用电子显微镜技术分析寄生虫的形态和超微结构。ATZ−S-04 化合物在两项测试中均显示出最佳结果。其在前鞭毛体、纯无鞭毛体和细胞内无鞭毛体中的IC 50分别为0.35±0.08 μM、0.49±0.06 μM和15.90±2
• 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.
• 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.