5α-cholestan-6-one thiosemicarbazone | 189566-94-7

• 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: 5α-cholestan-6-one thiosemicarbazone
• CAS: 189566-94-7
• 化学式: C₂₈H₄₉N₃S
• 分子量: 459.783
• InChiKey: SWOPWSLYYUWLRG-YYIXTDKQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  32.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  50.41
• 氢给体数：
  2.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  5α-cholestan-6-one thiosemicarbazone 在 间氯过氧苯甲酸 作用下， 以 氯仿 为溶剂， 以68%的产率得到5α-cholestan-6-spiro-1',2',4'-triazolidine-3'-thione
  参考文献：
  名称：

  Salim, Shamsuzzaman Anwar; Saleem, Kishwar; Khan, Mukhtar A., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1997, vol. 36, # 7, p. 617 - 619

  摘要：

  DOI：
• 作为产物：
  描述：

  5α-cholestan-6-one 、 氨基硫脲 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 5.0h， 生成 5α-cholestan-6-one thiosemicarbazone
  参考文献：
  名称：

  甾类咪唑：合成，表征，分子对接研究与DNA和体外细胞毒性

  摘要：

  具有生物活性的甾族咪唑7 – 9是通过使甾族硫代半碳杂唑酮4 – 6与苯甲酰溴反应而合成的。通过光谱和分析数据表征后，通过紫外可见光谱，发光光谱和凝胶电泳进行化合物7 – 9与DNA的相互作用。化合物通过与K b的静电和疏水相互作用优先与DNA结合; 3.14×10 4，6.27×10 4和5.17×10 4 中号-1，分别指示更高化合物的结合亲和力8对DNA。凝胶电泳描述了具有超螺旋pBR322的化合物8的浓度依赖性切割活性。对接研究揭示了化合物与DNA的微小凹槽结合，核苷酸碱基对之间的插入是由于咪唑部分。在二甲基噻唑基二苯基溴化四氮唑测定中，化合物7和8对不同的人类癌细胞，特别是对A545，HepG2和MCF7细胞具有活性。通过共聚焦显微镜研究了HepG2，MCF7和A549细胞对化合物的摄取。化合物7和8的遗传毒性 通过彗星试验研究了该蛋白，同时通过蛋白质印迹分析研究了与甾族咪唑相互作用后A545细胞凋亡标记的相对表达。

  DOI：

  10.1007/s00044-016-1755-z

文献信息

• Spectroscopic, Viscositic, DNA Binding and Cytotoxic Studies of Newly Synthesized Steroidal Imidazolidines
  作者：Ayaz Mahmood Dar、Shamsuzzaman、Shakir Khan

  DOI：10.1007/s10895-015-1750-7

  日期：2016.3

  A series of new steroidal imidazolidine derivatives (4–6) were synthesized after reacting steroidal thiosemicarbazones with chloro ethylacetate in absolute ethanol. After characterization by spectral and analytical data, the interaction studies of compounds (4–6) with DNA were carried out by UV–vis, fluorescence spectroscopy, hydrodynamic measurements, molecular docking and gel electrophoresis. The compounds bind to DNA preferentially through electrostatic and hydrophobic interactions with Kb; 2.63 × 103 M−1, 1.81 × 103 M−1 and 2.06 × 103 M−1, respectively indicating the higher binding affinity of compound 4 towards DNA. Gel electrophoresis demonstrated that compound 4 showed strong interaction during the concentration dependent cleavage activity with pBR322 DNA. The molecular docking study suggested the intercalation of imidazolidine moiety of steroid derivative in minor groove of DNA. During in vitro cytotoxicity, compounds (4–6) revealed potential toxicity against the different human cancer cells (MTT assay). The uptake of compound 4 by MCF-7 and HeLa cells was studied by confocal microscopy which determined cell shrinkage and hence leading to the apoptosis. The results revealed that compound 4 has better prospectus to act as cancer chemotherapeutic candidate which warrants further in vivo anticancer investigations.

  一系列新的甾体咪唑啉衍生物（4-6）在用氯乙酸乙酯在绝对乙醇中反应甾体硫代缩氨基脲后合成。通过光谱和分析数据表征后，通过紫外-可见光谱、荧光光谱、流体力学测量、分子对接和凝胶电泳研究了化合物（4-6）与DNA的相互作用。这些化合物通过静电和疏水相互作用优先与DNA结合，结合常数分别为2.63×10^3 M^-1、1.81×10^3 M^-1和2.06×10^3 M^-1，表明化合物4对DNA的结合亲和力更高。凝胶电泳显示，化合物4在浓度依赖的切割活性中与pBR322 DNA表现出强烈的相互作用。分子对接研究表明，甾体衍生物的咪唑啉部分插入DNA的小沟中。在体外细胞毒性研究中，化合物（4-6）对不同的人类癌细胞显示了潜在的毒性（MTT assay）。通过共聚焦显微镜研究了化合物4在MCF-7和HeLa细胞中的摄取，结果表明细胞收缩，从而导致凋亡。结果表明，化合物4有更好的前景作为癌症化疗候选药物，这需要进一步的在体抗癌研究。
• DNA Interaction Studies and In Vitro Cytotoxicity of Newly Synthesized Steroidal Imidazolidinones
  作者：Ayaz Mahmood Dar、Manzoor Ahmad Gatoo、Ajaz Ahmad、Mir Shabeer Ahmad、Muzaffar Hussain Najar、Shamsuzzaman

  DOI：10.1007/s10895-015-1628-8

  日期：2015.9

  New steroidal imidazolidinone derivatives (7–9) were synthesized after reacting steroidal thiosemicarbazones with oxalyl chloride in absolute ethanol. After characterization by spectral and analytical data, the interaction studies of compounds (7–9) with DNA were carried out by UV–vis, fluorescence spectroscopy, circular dichroism, molecular docking and gel electrophoresis. The compounds bind to DNA preferentially through electrostatic and hydrophobic interactions with Kb; 2.31 × 104 M−1, 2.57 × 104 M−1 and 2.16 × 104 M−1, respectively indicating the higher binding affinity of compound 8 towards DNA. Gel electrophoresis demonstrated that the compounds 7–9 show strong interaction during the cleavage activity with pBR322 DNA. The docking study suggested the intercalation of imidazolidinone moiety of steroid derivative in minor groove of DNA. During in vitro cytotoxicity, compounds 7–9 revealed potential toxicity against the different human cancer cells (MTT assay). Apoptotic degradation of DNA in presence of compounds 7–9 was analyzed by agarose gel electrophoresis and visualized by ethidium bromide staining (comet assay). FACS analysis shows that the compound 8 bring about cell cycle arrest at 7 μM concentration.

  新的类固醇咪唑烷酮衍生物（7–9）是在绝对乙醇中将类固醇硫脲与草酰氯反应后合成的。通过光谱和分析数据进行表征后，进行了化合物（7–9）与DNA的相互作用研究，采用了紫外可见光谱、荧光光谱、圆二色性分光法、分子对接和凝胶电泳等方法。结果表明，这些化合物通过静电和疏水相互作用优先与DNA结合，结合常数Kb分别为2.31×10^4 M−1、2.57×10^4 M−1和2.16×10^4 M−1，表明化合物8对DNA具有更高的结合亲和力。凝胶电泳显示化合物7–9在pBR322 DNA断裂活性中表现出强相互作用。对接研究表明，类固醇衍生物的咪唑烷酮部分嵌入在DNA的小沟中。在体外细胞毒性实验中，化合物7–9显示出对不同人癌细胞（MTT测定）的潜在毒性。在存在化合物7–9的情况下，使用琼脂糖凝胶电泳分析了DNA的凋亡降解，并通过溴化乙锭染色（彗星实验）可视化。FACS分析显示，化合物8在7μM浓度下引起细胞周期停滞。
• DNA binding, docking studies, artificial nuclease activity and in vitro cytotoxicity of newly synthesized steroidal 1H–pyrimidines
  作者：Shamsuzzaman、Ayaz Mahmood Dar、Sartaj Tabassum、Mehvash Zaki、Yusuf Khan、Aamir Sohail、Manzoor Ahmad Gatoo

  DOI：10.1016/j.crci.2013.07.001

  日期：2014.4

  Résumé A new series of steroidal pyrimidines (7–9) has been synthesized by reacting steroidal thiosemicarbazones (4–6) with ethyl cyanoacetate. The compounds were characterized by IR, 1H NMR, 13C NMR, MS and analytical data. The interaction studies of compounds 7–9 with DNA were carried out by UV–vis and luminescence spectroscopy. Compounds (7–9) bind to DNA preferentially through electrostatic and hydrophobic interactions, with Kb values found to be 6.56 × 103 M−1, 1.54 × 104 M−1 and 9.34 × 103 M−1, respectively, indicating the higher binding affinity of compound 8 towards DNA. Gel electrophoresis pattern demonstrated that compound 8 shows strong interaction with DNA and that, during its cleavage activity with pBR322 DNA, it seems to follow the mechanistic pathway involving the generation of singlet oxygen and a superoxide anion, which are responsible for initiating DNA strand scission. The docking study suggested that the intercalation of compounds in between the nucleotide base pairs is due to the presence of a pyrimidine moiety in the steroid molecule. MTT assay was carried out to check the toxicity of new compounds 7–9 against the different human cancer as well as non-cancer cell lines A545, MCF-7, HeLa, HL-60, SW480, HepG2, HT-29, A549, 184B5, MCF10A, NL-20, HPC, and HPLF. Apoptotic degradation of DNA in the presence of steroidal pyrimidines 7–9 was analysed by agarose gel electrophoresis and visualized by ethidium bromide staining (comet assay).

  摘要 一系列类固醇嘧啶（7-9）通过将类固醇硫半脲酮（4-6）与乙基氰乙酸酯反应合成。该化合物通过红外光谱（IR）、氢核磁共振（1H NMR）、碳核磁共振（13C NMR）、质谱（MS）和分析数据进行了表征。对化合物7-9与DNA的相互作用研究通过紫外-可见光（UV-vis）和荧光光谱法进行。化合物（7-9）通过静电和疏水相互作用优先结合DNA，Kb值分别为6.56×10^3 M−1、1.54×10^4 M−1和9.34×10^3 M−1，表明化合物8对DNA的结合亲和力较高。凝胶电泳模式表明化合物8与DNA具有强相互作用，并且在与pBR322 DNA的切割活性中，似乎遵循包含单线态氧和超氧阴离子产生的机制路径，这些物质负责启动DNA链断裂。对接研究表明化合物插入核苷酸碱基对之间是由于类固醇分子中存在嘧啶部分。MTT测定用于检查新化合物7-9对不同人类癌症及非癌细胞系（如A545、MCF-7、HeLa、HL-60、SW480、HepG2、HT-29、A549、184B5、MCF10A、NL-20、HPC和HPLF）的毒性。在类固醇嘧啶7-9存在下，DNA的凋亡降解通过琼脂糖凝胶电泳分析，并通过溴化乙锭染色（彗星实验）可视化。
• SINGLE-STEP SYNTHESIS, CHARACTERIZATION AND ANTIMICROBIAL STUDIES OF NOVEL STEROIDAL 1', 2', 3'- THIADIAZOLES
  作者：NAZISH SIDDIQUI、SHAMSUZZAMAN

  DOI：10.4067/s0717-97072013000300031

  日期：——

  thiadiazoles, Semicarbazones, thiosemicarbazones, Thionyl chloride, Antimicrobial activity. e-mail: [e-mail] INTRODUCTION Recent studies reveals that incorporation of hetero atom (N/O/S) enhances the biological activities of steroidal molecules. The importance of heterocyclic compounds has long been recognized in the field of synthetic organic chemistry and thiadiazoles are well documented,

  摘要已经报道了由甾族6-酮半咔唑1-3与亚硫酰氯方便地一步合成甾族噻二唑7-9。在相似的反应条件下，甾体6-酮硫代半碳氮酮4-6也提供了相同的产物7-9。这些新合成的化合物的结构是根据其IR，1 H NMR和13 C NMR，元素和分析数据确定的。筛选合成的化合物对不同细菌（革兰氏阳性和革兰氏阴性）和真菌菌株的体外抗菌活性。所有合成的化合物均显示出对各种微生物的显着活性。关键字：甾族噻二唑，氨基脲，硫代半氨基甲酮，亚硫酰氯，抗菌活性。电子邮件：nazish_sadat @ rediffmail。com引言最近的研究表明，掺入杂原子（N / O / S）可以增强甾体分子的生物活性。杂环化合物的重要性早已在合成有机化学领域中被认识到，噻二唑已被充分记录，尤其是在发现某些噻二唑与多种生理活性（例如抗黄曲霉毒素）有关的发现之后
• DNA binding, artificial nuclease activity and cytotoxic studies of newly synthesized steroidal pyrimidines
  作者：Ayaz Mahmood Dar、Bilal Rah、Shafia Mir、Rizwan Nabi、Shamsuzzaman、Manzoor Ahmad Gatoo、Ashraf Mashrai、Yusuf Khan

  DOI：10.1016/j.ijbiomac.2017.12.128

  日期：2018.5

  compound 4 towards DNA. Gel electrophoresis demonstrated that compound 4 showed a strong interaction during the concentration dependent cleavage activity with pBR322 DNA. The molecular docking study suggested the intercalation of steroidal pyrimidine moiety in the minor groove of DNA. During in vitro cytotoxicity, compounds (4–6) revealed potential toxicity against the different human cancer cells (MTT

  新的甾族嘧啶衍生物（4–6）是通过甾族硫代半脲酮与（2-甲基）丙二酸二乙酯在无水乙醇中的反应合成的。通过光谱和分析数据表征后，通过紫外可见光谱，荧光光谱，流体力学测量，分子对接和凝胶电泳对化合物（4–6）的DNA相互作用进行了研究。这些化合物优先通过与K b的静电和疏水相互作用与DNA结合; 2.31×10 3  M - 1，1.93×10 3  M -1和2.05×10 3  M -1分别表明化合物的结合亲和力更高4朝DNA方向发展。凝胶电泳表明，化合物4在与pBR322 DNA的浓度依赖性裂解活性过程中表现出强相互作用。分子对接研究表明，甾族嘧啶部分插入了DNA的小沟中。在体外细胞毒性过程中，化合物（4–6）显示出对不同人类癌细胞的潜在毒性（MTT分析）。在DAPI染色过程中，用化合物4和5处理后，细胞上发生了核碎裂。Western印迹分析清楚地表明化合物4引起MCF-7癌细胞的凋亡。结果表明，化合物4