3,4-dichlorobenzaldehyde semicarbazone

• 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: 3,4-dichlorobenzaldehyde semicarbazone
• 英文别名: m,p-dichlorobenzaldehyde semicarbazone；[(3,4-Dichlorophenyl)methylideneamino]urea
• 化学式: C₈H₇Cl₂N₃O
• mdl: MFCD00928625
• 分子量: 232.069
• InChiKey: MSPDWOWDLGZHHQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  67.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3,4-dichlorobenzaldehyde semicarbazone 在 碘 、 potassium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 以86%的产率得到5-(3,4-dichlorophenyl)-1,3,4-oxadiazol-2-amine
  参考文献：
  名称：

  一系列新型 2-氨基 5-取代的 1,3,4-恶二唑和 1,3,4-噻二唑衍生物的合成，作为潜在的抗癌剂、抗真菌剂和抗菌剂。

  摘要：

  背景技术许多含有五元杂环的化合物显示出特殊的化学性质和多种生物活性。目的本研究的目的是制备5-取代2-氨基-1,3,4-恶二唑和2-氨基-1,3,4-噻二唑衍生物并评价其潜在的抗癌、抗菌和抗真菌活性。方法通过碘介导的氨基脲或氨基硫脲与醛缩合得到的氨基脲或氨基氨基硫脲环化合成27个衍生物。结构通过1H-NMR、13C-NMR和MS光谱证实。采用扩散法评价抗菌和抗真菌活性，采用MTT法评价抗癌活性。结果 以中等至良好的产率合成了 27 种衍生物。许多衍生物表现出潜在的抗菌、抗真菌和抗癌活性。结论化合物(1b、1e和1g)对粪链球菌、MSSA和MRSA具有抗菌活性，MIC值在4～64 μg/mL之间。化合物（2g）对白色念珠菌（8μg/mL）和黑曲霉（64μg/mL）显示出抗真菌活性。化合物(1o)对HepG2细胞系表现出高细胞毒活性(IC50值为8.6 μM)，与紫杉醇的活性相当，对LLC-P

  DOI：

  10.2174/1573406417666210803170637
• 作为产物：
  描述：

  盐酸氨基脲 、 3,4-二氯苯甲醛 在 sodium acetate 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 3,4-dichlorobenzaldehyde semicarbazone
  参考文献：
  名称：

  通过NBS介导的缩氨基脲氧化环化超声辅助合成2-氨基-1,3,4-恶二唑

  摘要：

  摘要 建立了在乙酸钠存在下使用 N-溴代琥珀酰亚胺进行缩氨基脲的超声辅助氧化环化，提供了对各种 2-氨基-1,3,4-恶二唑的高效快速访问。此外，新的合成方案提供了一个简单的程序，利用更安全的氧化系统，以高区域选择性、令人满意的收率和更高的纯度提供目标产品。图形概要

  DOI：

  10.1080/00397911.2017.1324626

文献信息

• Synthesis, Antileishmanial Activity and in silico Studies of Aminoguanidine Hydrazones (AGH) and Thiosemicarbazones (TSC) Against Leishmania chagasi Amastigotes
  作者：Thiago M. de Aquino、Paulo H. B. França、Érica E. E. S. Rodrigues、Igor. J.S. Nascimento、Paulo F. S. Santos-Júnior、Pedro G. V. Aquino、Mariana S. Santos、Aline C. Queiroz、Morgana V. Araújo、Magna S. Alexandre-Moreira、Raiza R. L. Rodrigues、Klinger A. F. Rodrigues、Johnnatan D. Freitas、Jacques Bricard、Mario R. Meneghetti、Jean-Jacques Bourguignon、Martine Schmitt、Edeildo F. da Silva-Júnior、João X. de Araújo-Júnior

  DOI：10.2174/1573406417666210216154428

  日期：2022.2

  Leishmaniasis is a worldwide health problem, highly endemic in developing countries. Among the four main clinical forms of the disease, visceral leishmaniasis is the most severe, fatal in 95% of cases. The undesired side-effects from first-line chemotherapy and the reported drug resistance search for effective drugs that can replace or supplement those currently used an urgent need. Aminoguanidine hydrazones (AGH's) have been explored for exhibiting a diverse spectrum of biological activities, in particular the antileishmanial activity of MGBG. The bioisosteres thiosemicarbazones (TSC's) offer a similar biological activity diversity, including antiprotozoal effects against Leishmania species and Trypanosoma cruzi.

  Considering the impact of leishmaniasis worldwide, this work aimed to design, synthesize, and perform a screening upon L. chagasi amastigotes and for the cytotoxicity of the small "in-house" library of both AGH and TSC derivatives and their structurally-related compounds.

  A set of AGH's (3-7), TSC's (9, 10), and semicarbazones (11) were initially synthesized. Subsequently, different semi-constrained analogs were designed and also prepared, including thiazolidines (12), dihydrothiazines (13), imidazolines (15), pyrimidines (16, 18) azines (19, 20), and benzotriazepinones (23-25). All intermediates and target compounds were obtained with satisfactory yields and exhibited spectral data consistent with their structures. All final compounds were evaluated against L. chagasi amastigotes and J774.A1 cell line. Molecular docking was performed towards trypanothione reductase using GOLD® software.

  The AGH's 3i, 4a, and 5d, and the TSC's 9i, 9k, and 9o were selected as valuable hits. These compounds presented antileishmanial activity compared with pentamidine, showing IC50 values ranged from 0.6 to 7.27 μM, maximal effects up to 55.3%, and satisfactory SI values (ranged from 11 to 87). On the other hand, most of the resulting semi-constrained analogs were found cytotoxic or presented reduced antileishmanial activity. In general, TSC class is more promising than its isosteric AGH analogs, and the beneficial aromatic substituent effects are not similar in both series. In silico studies have suggested that these hits are capable of inhibiting the trypanothione reductase from the amastigote forms.

  The promising antileishmanial activity of three AGH’s and three TSC’s was characterized. These compounds presented antileishmanial activity compared with PTD, showing IC50 values ranged from 0.6 to 7.27 μM, and satisfactory SI values. Further pharmacological assays involving other Leishmania strains are under progress, which will help to choose the best hits for in vivo experiments.

  背景：利什曼病是全球性健康问题，在发展中国家高度流行。在该病的四种主要临床形式中，内脏利什曼病是最严重的，95%的病例会致命。由于一线化疗药物的不良副作用和报道的药物耐药性，迫切需要寻找可以替代或补充当前使用的有效药物。氨基胍脒肼酮（AGH）已被探索用于展示多样的生物活性，特别是MGBG的抗利什曼病活性。生物同功异构体硫脲半胱氨酮（TSC）提供类似的生物活性多样性，包括对利什曼病和克氏锥虫的抗原虫效应。 目的：考虑到利什曼病在全球范围内的影响，本研究旨在设计、合成并对L. chagasi阿马斯蒂果虫进行筛选，以及对小型“内部”AGH和TSC衍生物及其结构相关化合物的细胞毒性进行评估。 方法：首先合成了一组AGH（3-7）、TSC（9, 10）和半胱氨酮（11）。随后，设计并制备了不同的半约束类似物，包括噻唑烷（12）、二氢噻嗪（13）、咪唑烷（15）、嘧啶（16, 18）、吲哚烷（19, 20）和苯并三唑环酮（23-25）。所有中间体和目标化合物均以满意的收率获得，并展示了与其结构一致的光谱数据。所有最终化合物均对L. chagasi阿马斯蒂果虫和J774.A1细胞系进行了评估。使用GOLD®软件对其进行了针对巯基还原酶的分子对接。 结果：AGH的3i、4a和5d以及TSC的9i、9k和9o被选为有价值的命中物。这些化合物与五环胺相比具有抗利什曼病活性，IC50值范围从0.6到7.27μM，最大效果高达55.3％，满意的SI值（范围从11到87）。另一方面，大多数结果的半约束类似物被发现具有细胞毒性或具有降低的抗利什曼病活性。总体而言，TSC类比其同功异构AGH类更有前景，而有益的芳香族取代作用在两个系列中并不相似。计算机模拟研究表明这些命中物能够抑制阿马斯蒂果虫的巯基还原酶。 结论：三种AGH和三种TSC的有前景的抗利什曼病活性得到了表征。这些化合物与PTD相比具有抗利什曼病活性，IC50值范围从0.6到7.27μM，SI值满意。正在进行涉及其他利什曼病菌株的进一步药理学评估，这将有助于选择最佳的命中物进行体内实验。
• Ultrasound-assisted synthesis of 2-amino-1,3,4-oxadiazoles through NBS-mediated oxidative cyclization of semicarbazones
  作者：Ana Flávia Borsoi、Mateus Emanuel Coldeira、Kenia Pissinate、Fernanda Souza Macchi、Luiz Augusto Basso、Diógenes Santiago Santos、Pablo Machado

  DOI：10.1080/00397911.2017.1324626

  日期：2017.7.18

  ABSTRACT A ultrasound-assisted oxidative cyclization of semicarbazones using N-bromosuccinimide in the presence of sodium acetate was established providing efficient and rapid access to a variety of 2-amino-1,3,4-oxadiazoles. Moreover, the new synthetic protocol provides a simple procedure utilizing a safer oxidizing system that affords the target products in high regioselectivity, satisfactory yields

  摘要 建立了在乙酸钠存在下使用 N-溴代琥珀酰亚胺进行缩氨基脲的超声辅助氧化环化，提供了对各种 2-氨基-1,3,4-恶二唑的高效快速访问。此外，新的合成方案提供了一个简单的程序，利用更安全的氧化系统，以高区域选择性、令人满意的收率和更高的纯度提供目标产品。图形概要
• Biological Evaluation of Arylsemicarbazone Derivatives as Potential Anticancer Agents
  作者：Anne Cecília Nascimento da Cruz、Dalci José Brondani、Temístocles I´talo de Santana、Lucas Oliveira da Silva、Elizabeth Fernanda da Oliveira Borba、Antônio Rodolfo de Faria、Julianna Ferreira Cavalcanti de Albuquerque、Sylvie Piessard、Rafael Matos Ximenes、Blandine Baratte、Stéphane Bach、Sandrine Ruchaud、Francisco Jaime Bezerra Mendonça Junior、Marc-Antoine Bazin、Marcelo Montenegro Rabello、Marcelo Zaldini Hernandes、Pascal Marchand、Teresinha Gonçalves da Silva

  DOI：10.3390/ph12040169

  日期：——

  Fourteen arylsemicarbazone derivatives were synthesized and evaluated in order to find agents with potential anticancer activity. Cytotoxic screening was performed against K562, HL-60, MOLT-4, HEp-2, NCI-H292, HT-29 and MCF-7 tumor cell lines. Compounds 3c and 4a were active against the tested cancer cell lines, being more cytotoxic for the HL-60 cell line with IC50 values of 13.08 μM and 11.38 μM

  合成并评估了十四种芳基半碳a酮衍生物，以发现具有潜在抗癌活性的药物。针对K562，HL-60，MOLT-4，HEp-2，NCI-H292，HT-29和MCF-7肿瘤细胞系进行细胞毒性筛选。化合物3c和4a对测试的癌细胞系具有活性，对HL-60细胞系具有更大的细胞毒性，IC50值分别为13.08μM和11.38μM。关于蛋白激酶抑制试验，3c抑制7种不同的激酶，4a强烈抑制CK1δ/ε激酶。研究的激酶参与多种细胞功能，例如增殖，迁移，细胞死亡和细胞周期进程。通过流式细胞仪进行的其他分析显示3c和4a引起线粒体膜去极化，表明由内在途径介导的细胞凋亡。化合物3c诱导了HL-60细胞在细胞周期的G1期停滞，在膜联蛋白V试验中，约50％的细胞在最高测试浓度（26μM）下处于凋亡状态。化合物4a通过在G1期聚集异常的有丝分裂后细胞来抑制细胞周期，并以最高浓度（22μM）诱导DNA片段化。
• Pizzo, Chiara; Faral-Tello, Paula; Yaluff, Gloria, European Journal of Medicinal Chemistry, 2016, vol. 109, p. 107 - 113
  作者：Pizzo, Chiara、Faral-Tello, Paula、Yaluff, Gloria、Serna, Elva、Torres, Susana、Vera, Ninfa、Saiz, Cecilia、Robello, Carlos、Mahler, Graciela

  DOI：——

  日期：——
• Thiosemicarbazones as Aedes aegypti larvicidal
  作者：João Bosco P. da Silva、Daniela Maria do A.F. Navarro、Aluizio G. da Silva、Geanne K.N. Santos、Kamilla A. Dutra、Diogo Rodrigo Moreira、Mozart N. Ramos、José Wanderlan P. Espíndola、Ana Daura T. de Oliveira、Dalci José Brondani、Ana Cristina L. Leite、Marcelo Zaldini Hernandes、Valéria R.A. Pereira、Lucas F. da Rocha、Maria Carolina A.B. de Castro、Beatriz C. de Oliveira、Que Lan、Kenneth M. Merz

  DOI：10.1016/j.ejmech.2015.04.061

  日期：2015.7

  A set of aryl- and phenoxymethyl-(thio)semicarbazones were synthetized, characterized and biologically evaluated against the larvae of Aedes aegypti (A. aegypti), the vector responsible for diseases like Dengue and Yellow fever. (Q)SAR studies were useful for predicting the activities of the compounds not included to create the QSAR model as well as to predict the features of a new compound with improved activity. Docking studies corroborated experimental evidence of AeSCP-2 as a potential target able to explain the larvicidal properties of its compounds. The trend observed between the in silica Docking scores and the in vitro pLC50 (equals -log LC50, at molar concentration) data indicated that the highest larvicidal compounds, or the compounds with the highest values for pLC50, are usually those with the higher docking scores (i.e., greater in silica affinity for the AeSCP-2 target). Determination of cytotoxicity for these compounds in mammal cells demonstrated that the top larvicide compounds are non-toxic. (C) 2015 Elsevier Masson SAS. All rights reserved.