(E)-3′-bromoacetophenone thiosemicarbazone

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (E)-3′-bromoacetophenone thiosemicarbazone
• 英文别名: 3'-bromoacetophenone thio semicarbazone；[(E)-1-(3-bromophenyl)ethylideneamino]thiourea
• 化学式: C₉H₁₀BrN₃S
• 分子量: 272.168
• InChiKey: WJQYKRIBWNZUHM-WUXMJOGZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  82.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (E)-3′-bromoacetophenone thiosemicarbazone 在 盐酸羟胺 、 sodium hydride 、 potassium hydroxide 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 14.08h， 生成 (E)-N-hydroxy-6-(2-(1-(3-bromophenyl)ethylidene)hydrazin-1-ylthiocarbonylamino)hexanamide
  参考文献：
  名称：

  Discovery of thiosemicarbazone-containing compounds with potent anti-proliferation activity against drug-resistant K562/A02 cells

  摘要：

  P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) is a major obstacle to successful chemotherapy for leukemia. In this study, a series of thiosemicarbazone-containing compounds (4a-b, 7a-q) were synthesized. Biological evaluation showed that the most active compound 7e displayed potent anti-leukemia activity against P-gp overexpressing drug-resistant K562/A02 cells, with an IC₅₀ value of 0.44 μM. Notably, compound 7e exhibited a selective killing effect on K562/A02 cells by dose-dependently increasing the intracellular levels of reactive oxygen species (ROS), thus exerting a potential collateral sensitivity (CS)-promoting effect in vitro. Moreover, compound 7e could inhibit HDAC1 and HDAC6, and induce the apoptosis of K562/A02 cells by increasing the expression of Bax, decreasing Bcl-2 protein level, and promoting the cleavage of caspase-3 and PARP, respectively. Overall, 7e may be a potential anti-cancer agent against drug-resistant myelogenous leukemia.

  DOI：

  10.1016/j.bmcl.2020.127638
• 作为产物：
  描述：

  氨基硫脲 、 3'-溴苯乙酮 以 乙醇 为溶剂， 反应 8.0h， 以78%的产率得到(E)-3′-bromoacetophenone thiosemicarbazone
  参考文献：
  名称：

  卤代芳香族硫半脲类作为酪氨酸酶和黑色素生成的有效抑制剂。

  摘要：

  已经合成了一组21个卤代硫代半氨基甲酮（TSC），并研究了其对蘑菇酪氨酸酶活性双酚酶的抑制特性以及它们在B16F10小鼠黑素瘤细胞系中抑制黑素生成的能力。还进行了与酶活性位点的分子对接，以研究酶-抑制剂相互作用的性质。获得的结果使我们能够进行SAR分析。TSC 6、12和21表现出最强的抑制特性，IC50分别为0.5、0.9和0.8 µM。他们揭示了酪氨酸酶抑制作用的可逆性和竞争性方式。根据SAR分析，在所研究的化合物中，硫代半氨基甲酮的对位取代的苯乙酮衍生物对该酶具有最高的亲和力。B16F10细胞中黑色素的产生被所有研究的化合物以微摩尔水平抑制。建议的抑制机理是基于硫代半氨基甲酮的硫脲部分的硫原子与酶活性位点中的铜离子之间的相互作用。这些结果可能有助于寻找可用于化妆品和食品工业的新型黑色素生成抑制剂。

  DOI：

  10.1016/j.bioorg.2019.103419

文献信息

• [EN] ANTI-PARASITIC COMPOUNDS AND METHODS OF THEIR USE<br/>[FR] COMPOSES ANTIPARASITAIRES ET LEURS PROCEDES D'UTILISATION
  申请人：UNIV CALIFORNIA

  公开号：WO2005087211A1

  公开（公告）日：2005-09-22

  The present invention provides a novel class of compounds that disrupt the parasitic infectious life cycle and serve as promising agents for anti-parasitic therapy.

  本发明提供了一类新型化合物，可以破坏寄生虫的传染生命周期，并作为抗寄生虫疗法的有希望的药物。
• Thio semicarbazone and semicarbazone inhibitors of cysteine proteases and methods of their use
  申请人：The Regents of the University of California

  公开号：US20040014801A1

  公开（公告）日：2004-01-22

  The present invention relates to thio semicarbazone and semicarbazone inhibitors of cysteine proteases and methods of using such compounds to prevent and treat protozoan infections such as trypanosomiasis, malaria and leishmaniasis. The compounds also find use in inhibiting cysteine proteases associated with carcinogenesis, including cathepsins B and L.

  本发明涉及硫代半卡巴酮和半卡巴酮对半胱氨酸蛋白酶的抑制剂，以及使用这些化合物预防和治疗原生动物感染，如锥虫病、疟疾和利什曼病的方法。这些化合物还可用于抑制与癌变有关的半胱氨酸蛋白酶，包括卡特普辛B和L。
• Synthesis and Structure−Activity Relationship Study of Potent Trypanocidal Thio Semicarbazone Inhibitors of the Trypanosomal Cysteine Protease Cruzain
  作者：Xiaohui Du、Chun Guo、Elizabeth Hansell、Patricia S. Doyle、Conor R. Caffrey、Tod P. Holler、James H. McKerrow、Fred E. Cohen

  DOI：10.1021/jm010459j

  日期：2002.6.1

  American trypanosomiasis, or Chagas' disease, is the leading cause of heart disease in Latin America. Currently there is an urgent need to develop antitrypanosomal therapy due to the toxicity of existing agents and emerging drug resistance. A novel series of potent thio semicarbazone small-molecule inhibitors of the Trypanosoma cruzi cysteine protease cruzain have been identified. Some of these inhibitors have been shown to be trypanocidal. We initially discovered that X-bromopropiophenone thio semicarbazone (1i) inhibited cruzain and could cure mammalian cell cultures infected with T cruzi. 3'-Bromopropiophenone thio semicarbazone showed no toxicity for mammalian cells at concentrations that were trypanocidal. Following this lead, more than 100 compounds were designed and synthesized. A specific structure-activity relationship (SAR) was established, and many potent analogues with IC50 values in the low nanomolar range were identified. Eight additional analogues were trypanocidal in a cell culture assay, and this indicates that aryl thio semicarbazone is a productive scaffold for killing the parasites. Kinetic studies show that these are time-dependent inhibitors. Molecular modeling studies of the enzyme-inhibitor complex have led to a proposed mechanism of interaction as well as insight into the SAR of the thio semicarbazone series. The nonpeptide nature of this series, small size, and extremely low cost of production suggest this is a promising direction for the development of new antitrypanosome chemotherapy.
• Synthesis and Structure−Activity Relationships of Parasiticidal Thiosemicarbazone Cysteine Protease Inhibitors against <i>Plasmodium falciparum</i>, <i>Trypanosoma brucei</i>, and <i>Trypanosoma cruzi</i>
  作者：Doron C. Greenbaum、Zachary Mackey、Elizabeth Hansell、Patricia Doyle、Jiri Gut、Conor R. Caffrey、Julia Lehrman、Philip J. Rosenthal、James H. McKerrow、Kelly Chibale

  DOI：10.1021/jm030549j

  日期：2004.6.1

  We have synthesized a library of thiosemicarbazones and screened them against three parasitic cysteine proteases, cruzain, falcipain-2, and rhodesain, and against the respective parasite sources of these three proteases, Trypanosoma cruzi, Plasmodium falciparum, and Trypanosoma brucei. The screens identified compounds that were effective against the enzymes and the parasites but also some compounds that were parasiticidal despite a lack of activity against the proteases. Several compounds were effective in killing all tested parasites. These promising lead compounds were tested for general toxicity in mice, and only one produced observable toxicity after 62 h. Our results suggest that thiosemicarbazones represent validated drug leads that kill several species of protozoan parasites through the inhibition of cysteine proteases as well as other novel targets.
• ANTI-PARASITIC COMPOUNDS AND METHODS OF THEIR USE
  申请人：The Regents of the University of California

  公开号：EP1734939A1

  公开（公告）日：2006-12-27