(E)-3-(3-hydroxy-4-methoxyphenyl)-2-methyl-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: (E)-3-(3-hydroxy-4-methoxyphenyl)-2-methyl-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
• 英文别名: SD400；3-(3-Hydroxy-4-methoxyphenyl)-2-methyl-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
• 化学式: C₂₀H₂₂O₆
• 分子量: 358.391
• InChiKey: ZCMJTMRUBOCGSY-XYOKQWHBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  74.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (E)-3-(3-hydroxy-4-methoxyphenyl)-2-methyl-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one 在 盐酸 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 生成 (E)-N-hydroxy-6-(2-methoxy-5-(2-methyl-3-oxo-3-(3,4,5-trimethoxyphenyl)prop-1-en-1-yl)phenoxy)hexanamide
  参考文献：
  名称：

  Anti-tumor activity evaluation of novel tubulin and HDAC dual-targeting inhibitors

  摘要：

  Histone deacetylases (HDACs) have proven to be promising targets for the development of anti-cancer drugs. In this study, we reported a series of novel chalcone based tubulin and HDAC dual-targeting inhibitors. Three compounds inhibited the activities of HDAC and tubulin polymerization simultaneously and displayed anti-proliferative activities toward eleven human tumor cell lines. Compound 8a remarkably induced growth inhibition, apoptosis and G2/M phase arrest of A549 tumor cells. Finally, the inhibitory activities of 8a against HDAC6 and tubulin were rationalized by molecular docking studies.

  DOI：

  10.1016/j.bmcl.2019.07.045
• 作为产物：
  描述：

  1-(3,4,5-三甲氧基苯基)-1-丙醇 在 哌啶 、 草酰氯 、 溶剂黄146 、 二甲基亚砜 、 三乙胺 作用下， 以 乙醇 为溶剂， 反应 50.0h， 生成 (E)-3-(3-hydroxy-4-methoxyphenyl)-2-methyl-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
  参考文献：
  名称：

  Potent antimitotic and cell growth inhibitory properties of substituted chalcones

  摘要：

  A series of substituted chalcones was synthesised and screened for cytotoxic activity against the K562 human leukaemia cell line. (E)-3-(3"-Hydroxy-4"-methoxyphenyl)-2-methyl-1-(3',4',5'-trimethoxyphenyl)-prop-2-en-1-one [IC50 (K562) 0.21 nM] was found to be the most active. A relationship between the conformation and cytotoxicity of the chalcones is discussed. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00162-0

文献信息

• 一种组蛋白去乙酰化酶和微管双靶点抑制剂及其制备方法
  申请人：青岛大学

  公开号：CN109651199B

  公开（公告）日：2022-01-04

  本发明公开了一种组蛋白去乙酰化酶和微管双靶点抑制剂及其制备方法，该抑制剂如I)或II)所示：该抑制剂同时具有微管和组蛋白去乙酰化酶的双重抑制活性。
• MODIFIED CHALCONE COMPOUNDS AS ANTIMITOTIC AGENTS
  申请人：ROSE Seth D.

  公开号：US20070265317A1

  公开（公告）日：2007-11-15

  Antimitotic agents comprising a modified chalcone or modified chalcone derivative are disclosed. The modified chalcone or modified chalcone derivative compounds are of the general formula CHAL-LIN—COV, wherein CHAL is a chalcone or chalcone derivative portion, LIN is an optional linker portion, and COV is a covalent bonding portion (e.g., an α,β-unsaturated thiol ester group). The modified chalcone or modified chalcone derivative compounds provide an improved method of interference with tubulin polymerization, for example by covalent (and essentially irreversible) bonding between tubulin and the covalent bonding portion, potentially resulting in a decrease in tumor size and/or disappearance of the cancer, to the benefit of cancer patients.

  本发明涉及一种包含改性查尔酮或改性查尔酮衍生物的抗有丝分裂剂。改性查尔酮或改性查尔酮衍生物化合物的一般式为CHAL-LIN-COV，其中，CHAL是查尔酮或查尔酮衍生物部分，LIN是可选的连接部分，COV是共价键合部分（例如α，β-不饱和硫酯酯基）。改性查尔酮或改性查尔酮衍生物化合物提供了一种改进的干扰微管聚合的方法，例如通过微管和共价键合部分之间的共价键合（基本上是不可逆的），可能导致肿瘤大小减小和/或癌症消失，从而使癌症患者受益。
• Combretastatin a-4 derivatives having antineoplastic activity
  申请人：Lawrence James Nicholas

  公开号：US20050065213A1

  公开（公告）日：2005-03-24

  Compounds are disclosed that are designed to mimic the activity of combretastatin A-4 based on chalcone, aurone, or indanone structures, or involving benzoquinone or quinone rings. The anti-cancer activity of exemplified compounds is demonstrated in a range of in vitro and in vivo assays.

  公开了一些化合物，这些化合物是基于查尔酮、金合欢素或茚酮结构设计的，或涉及苯醌或醌环，旨在模仿紫杉醇A-4的活性。在一系列体外和体内试验中，展示了这些化合物的抗癌活性。
• 3,4-METHYLENEDIOXY-SUBSTITUTED CHALCONES AS THERAPEUTIC AGENTS
  申请人：Potter Gerard Andrew

  公开号：US20100028262A1

  公开（公告）日：2010-02-04

  The present invention pertains to the use of a compounds for the manufacture of a medicament for use in the treatment of a proliferative condition, wherein the compounds have the following formula: wherein: each of R B2 , R B3 , R B4 , and R B5 is independently —H, —OH, or —OMe; each of R 1 and R 2 is independently: —H, optionally substituted C 1-4 alkyl, or optionally substituted C 5-20 aryl; R A3 is —H, —OH, —OC(═O)R E , —OS(═O) 2 OH, or —OP(═O)(OH) 2 ; R E is: —H, optionally substituted C 1-6 alkyl, optionally substituted C 3-20 heterocyclyl, or optionally substituted C 5-20 aryl; or a pharmaceutically acceptable salt, solvate, amide, ester, ether, chemically protected form, or prodrug thereof. The present invention also pertains to such compounds, pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, for both diagnosis and treatment of, for example, proliferative conditions, such as cancer, and inflammatory conditions.

  本发明涉及使用化合物制备药物，用于治疗增殖性疾病，其中该化合物具有以下结构式：其中：RB2、RB3、RB4和RB5中的每一个独立地为—H、—OH或—OMe；R1和R2中的每一个独立地为—H、可选地取代的C1-4烷基或可选地取代的C5-20芳基；RA3为—H、—OH、—OC(═O)RE、—OS(═O)2OH或—OP(═O)(OH)2；RE为：—H、可选地取代的C1-6烷基、可选地取代的C3-20杂环基或可选地取代的C5-20芳基；或其药学上可接受的盐、溶剂化合物、酰胺、酯、醚、化学保护形式或前药。本发明还涉及这种化合物、包含这种化合物的药物组合物以及这种化合物和组合物的使用，无论是在体内还是体外，用于诊断和治疗增殖性疾病（例如癌症）和炎症性疾病。
• Combretastatin-like chalcones as inhibitors of microtubule polymerization. Part 1: Synthesis and biological evaluation of antivascular activity
  作者：Sylvie Ducki、David Rennison、Meiko Woo、Alexander Kendall、Jérémie Fournier Dit Chabert、Alan T. McGown、Nicholas J. Lawrence

  DOI：10.1016/j.bmc.2009.09.039

  日期：2009.11

  The alpha-methyl chalcone SD400 is a potent inhibitor of tubulin assembly and possesses potent anticancer activity. Various chalcone analogues were synthesized and evaluated for their cell growth inhibitory properties against the K562 human chronic myelogenous leukemia cell line (SD400, IC50 0.21 nM; combretastatin A4 CA4, IC50 2.0 nM). Cell cycle analysis by flow cytometry indicated that these agents are antimitotic (SD400, 83% of the cells are in G(2)/M phase; CA4 90%). They inhibit tubulin assembly at low concentration (SD400, IC50 0.46 mu M; CA4, 0.10 mu M) and compete with [H-3] colchicine for binding to tubulin (8% [H-3] colchicine remained bound to tubulin after competition with SD400 or CA4). Upon treatment with SD400, remarkable cell shape changes were elicited in HUVEC cells, consistent with vasculature damaging activity. (C) 2009 Elsevier Ltd. All rights reserved.