1-Phenyl-3-(2,4,5-trimethoxyphenyl)prop-2-en-1-one | 903676-65-3

• 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: 1-Phenyl-3-(2,4,5-trimethoxyphenyl)prop-2-en-1-one
• 英文别名: 1-phenyl-3-(2,4,5-trimethoxyphenyl)prop-2-en-1-one
• CAS: 903676-65-3
• 化学式: C₁₈H₁₈O₄
• mdl: MFCD04521004
• 分子量: 298.339
• InChiKey: SSCWRHWOQOBLJF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-Phenyl-3-(2,4,5-trimethoxyphenyl)prop-2-en-1-one 在 hydrazine hydrate 、 potassium carbonate 作用下， 以 甲醇 、 异丙醇 为溶剂， 反应 6.0h， 生成 methyl 3-phenyl-5-(2,4,5-trimethoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carboxylate
  参考文献：
  名称：

  一类新型的微管蛋白聚合抑制剂通过有丝分裂灾难发挥有效的抗肿瘤活性

  摘要：

  在当前工作中，设计，合成和评估了一类新型的4,5-二氢-1 H-吡唑-1-羧酸酯衍生物（E01-E28）。其中，最有效的化合物E24表现出相当的活性针对癌细胞的面板（GI 50测距0.05-0.98  μ M）和微管蛋白聚合的抑制（IC 50  = 1.49  μ M）参照药物CA-4（P）（GI 50测距0.019-0.32  μ男，IC 50  = 2.18  μ M）。以下测定表明化合物E24干扰了微管蛋白灾难性事件和抢救的动力学，从而触发了G2 / M阻滞，导致ROS积累，PARP裂解和细胞凋亡。分子动力学模拟验证了化合物E24可以紧密结合到微管蛋白异源二聚体与β的Lys 254和β在对接姿势微管蛋白的Cys的241。还确定了代谢稳定性和药代动力学参数。半衰期（t 1/2）显示了三个微粒体中的物种差异。血浆消除半衰期（t 1/2），血浆峰值浓度（C max），平均保留时间（MRT），曲线下面积（AUC0

  DOI：

  10.1016/j.ejmech.2018.12.030
• 作为产物：
  描述：

  顺式-2,4,5-三甲氧基-1-丙烯基苯 在 potassium permanganate 、 碳酸氢钠 、 potassium hydroxide 作用下， 以 乙醇 为溶剂， 生成 1-Phenyl-3-(2,4,5-trimethoxyphenyl)prop-2-en-1-one
  参考文献：
  名称：

  Synthesis of Unusually Substituted 2,4,5-Trimethoxy 3,5-Diaryl Isoxazoles from Natural Precursor: Antimicrobial and Anticancer Activities

  摘要：

  In this work, 2,4,5-trimethoxy substituted 3,5-diaryl isoxazoles were synthesized via their chalcone intermediates and evaluated for antimicrobial and anticancer activities. The natural precursor 2,4,5-trimethoxy benzaldehyde (asaronaldehyde) was obtained from oxidation of β-asarone (Acorus calamus oil) and then reacted with substituted acetophenones via Claisen-Schmidt condensation yielded 2,4,5-trimethoxy substituted chalcones. These chalcones on further treatment with hydroxylamine in presence of sodium acetate and acetic acid cyclizes to give the corresponding 3,5-diaryl isoxazoles yields ranging from 65-80%. Structures were confirmed by IR, GC-MS, 1H NMR and 13C NMR. Synthesized compounds were screened for their antimicrobial activity against bacteria and fungi. The para-substituted isoxazoles (5b, 5c and 5d) exhibited good activity against Gram-negative (Escherichia coli) and (Pseudomonas aeruginosa) and Gram-positive (Bacillus subtilis) and Bacillus licheniformis bacteria and fungi (Phytophthora capsici, Sclerotirum rolfsii, Aspergillus niger and Alternaria alternate). Further, these novel analogues were evaluated for their in vitro anticancer activity against three human tumor cell lines (MCF-7, SW-982 and HeLa) using MTT assay. The anticancer results revealed that phenyl ring at C-3 position bearing electron donor groups in the para-position and 2,4,5-trimethoxy substitutent of the phenyl ring at C-5 position isoxazole showed better inhibitory activity (5b, 5c and 5d). Among synthesized isoxazoles due to the hyper conjugative effect, 2,4,5-trimethoxy 3,5-diaryl isoxazole (5g) having 3-triflouromethyl substitution showed good antimicrobial and higher inhibitory IC50 values 8.56 ± 0.32, 12.16 ± 0.86 and 10.16 ± 0.68 μg/mL (p < 0.05) respectively, when compared to natural precursor β-asarone.

  DOI：

  10.14233/ajchem.2024.31015

文献信息

• Chalcone‐inspired <i>r</i> A ₁ /A _2A adenosine receptor ligands: Ring closure as an alternative to a reactive substructure
  作者：Chrisna Matthee、Gisella Terre’Blanche、Helena D. Janse van Rensburg、Janine Aucamp、Lesetja J. Legoabe

  DOI：10.1111/cbdd.13999

  日期：2022.3

  disease. Unfortunately, many of these compounds raise structure-related concerns. The present study investigated the effect of ring closures on the rA1/A2A affinity of compounds containing a highly reactive α,β-unsaturated carbonyl system, hence providing insight into the potential of heterocycles to address these concerns. A total of 12 heterocyclic compounds were synthesised and evaluated in silico

  在过去的几年中，高亲和力腺苷 A 1和/或 A 2A受体拮抗剂的开发取得了巨大进展——有望用于治疗帕金森病的潜在药物。不幸的是，许多这些化合物引起了与结构相关的问题。本研究调查了闭环对r A 1 /A 2A的影响含有高反应性 α,β-不饱和羰基系统的化合物的亲和力，因此可以深入了解杂环解决这些问题的潜力。共合成了 12 种杂环化合物，并在计算机和体外进行了评估。测试化合物在药物相似性的定性评估中表现良好，并且通常发现不含潜在的问题片段。大多数还表现出低/弱的细胞毒性。放射性配体结合实验的结果证实，杂环化合物（尤其是 2-取代的 3-氰基吡啶）可以取代混杂的 α,β-不饱和酮官能团而不损害 A 1 /A 2A亲和力。结构-活性关系突出了氢键在与感兴趣的受体结合中的重要性。化合物3c ( r A 1 K i  = 16 nM; r A 2A K i  = 65 nM) 和8a ( r A 1 K
• Pd-Catalyzed Cross-Coupling of Aryl Carboxylic Acids with Propiophenones through a Combination of Decarboxylation and Dehydrogenation
  作者：Jun Zhou、Ge Wu、Min Zhang、Xiaoming Jie、Weiping Su

  DOI：10.1002/chem.201200829

  日期：2012.6.25

  A Heck of a reaction: With a PCy3‐supported Pd catalyst, aryl carboxylic acids cross‐couple to saturated propiophenones through a combination of decarboxylation and dehydrogenation to give chalcones bearing a variety of functional groups in generally good yields (see scheme). Furthermore, a one‐pot procedure, involving this reaction and a subsequent selective hydrogenative cyclization process, has

  反应的难点：在PCy 3负载的Pd催化剂上，芳基羧酸通过脱羧和脱氢的组合与饱和的苯乙酮交联，以通常的高收率得到带有各种官能团的查耳酮（见方案）。此外，已经开发出一种涉及该反应和随后的选择性氢化环化过程的一锅法，用于从2-硝基苯甲酸轻松合成喹啉衍生物。
• Cytotoxic Effects on Breast Cancer Cell Lines of Chalcones Derived from a Natural Precursor and Their Molecular Docking Analysis
  作者：Luis Bustos、Carlos Echiburú-Chau、Alejandro Castro-Alvarez、Ben Bradshaw、Mario J. Simirgiotis、Marco Mellado、Claudio Parra、Mauricio Cuellar

  DOI：10.3390/molecules27144387

  日期：——

  This study aimed to determine the in vitro cytotoxicity and understand possible cytotoxic mechanisms via an in silico study of eleven chalcones synthesized from two acetophenones. Five were synthesized from a prenylacetophenone isolated from a plant that grows in the Andean region of the Atacama Desert. The cytotoxic activity of all the synthesized chalcones was tested against breast cancer cell lines using an MTT cell proliferation assay. The results suggest that the prenyl group in the A-ring of the methoxy and hydroxyl substituents of the B-ring appear to be crucial for the cytotoxicity of these compounds. The chalcones 12 and 13 showed significant inhibitory effects against growth in MCF-7 cells (IC50 4.19 ± 1.04 µM and IC50 3.30 ± 0.92 µM), ZR-75-1 cells (IC50 9.40 ± 1.74 µM and IC50 8.75 ± 2.01µM), and MDA-MB-231 cells (IC50 6.12 ± 0.84 µM and IC50 18.10 ± 1.65 µM). Moreover, these chalcones showed differential activity between MCF-10F (IC50 95.76 ± 1.52 µM and IC50 95.11 ± 1.97 µM, respectively) and the tumor lines. The in vitro results agree with molecular coupling results, whose affinity energies and binding mode agree with the most active compounds. Thus, compounds 12 and 13 can be considered for further studies and are candidates for developing new antitumor agents. In conclusion, these observations give rise to a new hypothesis for designing chalcones with potential cytotoxicity with high potential for the pharmaceutical industry.

  本研究旨在通过对两种苯乙酮合成的十一种查耳酮进行硅学研究，确定其体外细胞毒性并了解可能的细胞毒性机制。其中五种是从生长在阿塔卡马沙漠安第斯地区的一种植物中分离出来的前炔基苯乙酮合成的。利用 MTT 细胞增殖试验测试了所有合成的查耳酮对乳腺癌细胞株的细胞毒性活性。结果表明，甲氧基 A 环上的炔基和 B 环上的羟基取代基似乎是这些化合物产生细胞毒性的关键。查耳酮 12 和 13 对 MCF-7 细胞（IC50 4.19 ± 1.04 µM 和 IC50 3.30 ± 0.92 µM）、ZR-75-1 细胞（IC50 9.40 ± 1.74 µM 和 IC50 8.75 ± 2.01 µM）和 MDA-MB-231 细胞（IC50 6.12 ± 0.84 µM 和 IC50 18.10 ± 1.65 µM）的生长有显著的抑制作用。此外，这些查尔酮在 MCF-10F 细胞（IC50 分别为 95.76 ± 1.52 µM 和 IC50 95.11 ± 1.97 µM）和肿瘤株之间显示出不同的活性。体外结果与分子耦合结果一致，其亲和能和结合模式与最具活性的化合物一致。因此，可以考虑对化合物 12 和 13 进行进一步研究，并将其作为开发新型抗肿瘤药物的候选化合物。总之，这些观察结果为设计具有潜在细胞毒性的查耳酮提出了一个新的假设，具有很大的制药潜力。
• A class of novel tubulin polymerization inhibitors exert effective anti-tumor activity via mitotic catastrophe
  作者：Ya-Liang Zhang、Bo-Yan Li、Rong Yang、Lin-Ying Xia、A-Li Fan、Yi-Chun Chu、Lin-Jian Wang、Zhong-Chang Wang、Ai-Qin Jiang、Hai-Liang Zhu

  DOI：10.1016/j.ejmech.2018.12.030

  日期：2019.2

  In current work, a class of novel 4,5-dihydro-1H-pyrazole-1-carboxylate derivatives (E01-E28) were designed, synthesized and evaluated. Among them, the most potent compound E24 exhibited comparable activity against a panel of cancer cells (GI50 ranging 0.05–0.98 μM) and tubulin polymerization inhibition (IC50 = 1.49 μM) with reference drug CA-4(P) (GI50 ranging 0.019–0.32 μM, IC50 = 2.18 μM). The following

  在当前工作中，设计，合成和评估了一类新型的4,5-二氢-1 H-吡唑-1-羧酸酯衍生物（E01-E28）。其中，最有效的化合物E24表现出相当的活性针对癌细胞的面板（GI 50测距0.05-0.98  μ M）和微管蛋白聚合的抑制（IC 50  = 1.49  μ M）参照药物CA-4（P）（GI 50测距0.019-0.32  μ男，IC 50  = 2.18  μ M）。以下测定表明化合物E24干扰了微管蛋白灾难性事件和抢救的动力学，从而触发了G2 / M阻滞，导致ROS积累，PARP裂解和细胞凋亡。分子动力学模拟验证了化合物E24可以紧密结合到微管蛋白异源二聚体与β的Lys 254和β在对接姿势微管蛋白的Cys的241。还确定了代谢稳定性和药代动力学参数。半衰期（t 1/2）显示了三个微粒体中的物种差异。血浆消除半衰期（t 1/2），血浆峰值浓度（C max），平均保留时间（MRT），曲线下面积（AUC0
• Synthesis of Unusually Substituted 2,4,5-Trimethoxy 3,5-Diaryl Isoxazoles from Natural Precursor: Antimicrobial and Anticancer Activities
  作者：M.V. Ravindra、S. Suvarna、C.S. Ananda Kumar

  DOI：10.14233/ajchem.2024.31015

  日期：——

  In this work, 2,4,5-trimethoxy substituted 3,5-diaryl isoxazoles were synthesized via their chalcone intermediates and evaluated for antimicrobial and anticancer activities. The natural precursor 2,4,5-trimethoxy benzaldehyde (asaronaldehyde) was obtained from oxidation of β-asarone (Acorus calamus oil) and then reacted with substituted acetophenones via Claisen-Schmidt condensation yielded 2,4,5-trimethoxy substituted chalcones. These chalcones on further treatment with hydroxylamine in presence of sodium acetate and acetic acid cyclizes to give the corresponding 3,5-diaryl isoxazoles yields ranging from 65-80%. Structures were confirmed by IR, GC-MS, 1H NMR and 13C NMR. Synthesized compounds were screened for their antimicrobial activity against bacteria and fungi. The para-substituted isoxazoles (5b, 5c and 5d) exhibited good activity against Gram-negative (Escherichia coli) and (Pseudomonas aeruginosa) and Gram-positive (Bacillus subtilis) and Bacillus licheniformis bacteria and fungi (Phytophthora capsici, Sclerotirum rolfsii, Aspergillus niger and Alternaria alternate). Further, these novel analogues were evaluated for their in vitro anticancer activity against three human tumor cell lines (MCF-7, SW-982 and HeLa) using MTT assay. The anticancer results revealed that phenyl ring at C-3 position bearing electron donor groups in the para-position and 2,4,5-trimethoxy substitutent of the phenyl ring at C-5 position isoxazole showed better inhibitory activity (5b, 5c and 5d). Among synthesized isoxazoles due to the hyper conjugative effect, 2,4,5-trimethoxy 3,5-diaryl isoxazole (5g) having 3-triflouromethyl substitution showed good antimicrobial and higher inhibitory IC50 values 8.56 ± 0.32, 12.16 ± 0.86 and 10.16 ± 0.68 μg/mL (p < 0.05) respectively, when compared to natural precursor β-asarone.