3-hydroxy-2-(3-nitrophenyl)-4H-chromen-4-one | 107618-67-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: 3-hydroxy-2-(3-nitrophenyl)-4H-chromen-4-one
• 英文别名: 3-hydroxy-6-methyl-2-(3-nitrophenyl)chromen-4-one；3-hydroxy-2-(3-nitrophenyl)chromen-4-one
• CAS: 107618-67-7
• 化学式: C₁₅H₉NO₅
• 分子量: 283.24
• InChiKey: HQZRDBCJUWYZKY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  92.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-hydroxy-2-(3-nitrophenyl)-4H-chromen-4-one 、 氯化苄 在 四丁基溴化铵 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以74%的产率得到3-(benzyloxy)-2-(3-nitrophenyl)-4H-chromen-4-one
  参考文献：
  名称：

  探索 3-苄氧基黄酮作为新的先导胆碱酯酶抑制剂：合成、构效关系和分子建模模拟

  摘要：

  摘要 在该协议中，一系列 3-苄氧基黄酮衍生物已被设计、合成、表征和体外研究作为胆碱酯酶抑制剂。研究结果表明，所有合成的目标化合物 ( 1-10 ) 都是有效的乙酰胆碱酯酶 (AChE) 和丁酰胆碱酯酶 (BChE) 双重抑制剂，具有不同的 IC 50值。相比之下，它们对 AChE 的作用比 BChE 更有效。值得注意的是，除该系列中，化合物2被确定为既乙酰胆碱酯酶的最活跃的抑制剂（IC 50 = 0.05±0.01μM）和的BChE（IC 50 = 0.09±0.02μM）相对于标准多奈哌齐（IC 50= 0.09 ± 0.01（AChE）和 0.13 ± 0.04 μM（BChE）。此外，与标准品相比，衍生物5 (IC 50 = 0.07 ± 0.02 μM) 和10 (0.08 ± 0.02 μM) 对 AChE 表现出最高的选择性抑制。初步建立了构效关系，因此发现这些化合物的胆碱酯酶抑制活性高度依赖于

  DOI：

  10.1080/07391102.2020.1803136
• 作为产物：
  描述：

  1-(2-羟基苯基)-3-(3-硝基苯基)丙-2-烯-1-酮 在 双氧水 、 三乙胺 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 4.04h， 生成 3-hydroxy-2-(3-nitrophenyl)-4H-chromen-4-one
  参考文献：
  名称：

  在无溶剂条件下，由蒙脱土KSF粘土促进微波辐射辅助的黄酮醇的快速合成

  摘要：

  蒙脱石KSF粘土促进并辅助合成的2'-（甲氧基）环氧查尔酮（= 2-（3-芳基-2,3-环氧丙酰基）苯基甲磺酸盐）以简单，有效，快速且环保的方式合成黄酮醇，收率> 90％已经描述了通过微波辐射。

  DOI：

  10.1002/hlca.201200336

文献信息

• An Expeditious Synthesis of Flavonols Promoted by Montmorillonite KSF Clay and Assisted by Microwave Irradiation under Solvent-Free Conditions
  作者：Mariappan Babu、Kasi Pitchumani、Penugonda Ramesh

  DOI：10.1002/hlca.201200336

  日期：2013.7

  A simple, efficient, rapid, and ecofriendly synthesis of flavonols in >90% yield from 2′‐(mesyloxy)epoxychalcones (=2‐(3‐aryl‐2,3‐epoxypropanoyl)phenyl methanesulfonates) promoted by montmorillonite KSF clay and assisted by microwave irradiation has been described.

  蒙脱石KSF粘土促进并辅助合成的2'-（甲氧基）环氧查尔酮（= 2-（3-芳基-2,3-环氧丙酰基）苯基甲磺酸盐）以简单，有效，快速且环保的方式合成黄酮醇，收率> 90％已经描述了通过微波辐射。
• Identification of bicyclic compounds that act as dual inhibitors of Bcl-2 and Mcl-1
  作者：Abhay Uthale、Aarti Anantram、Prasad Sulkshane、Mariam Degani、Tanuja Teni

  DOI：10.1007/s11030-022-10494-6

  日期：——

  Elevated expression of anti-apoptotic proteins, such as Bcl-2 and Mcl-1 contributes to poor prognosis and resistance to current treatment modalities in multiple cancers. Here, we report the design, synthesis and characterization of benzimidazole chalcone and flavonoid scaffold-derived bicyclic compounds targeting both Bcl-2 and Mcl-1 by optimizing the structural differences in the binding sites of both these proteins. Initial docking screen of Bcl-2 and Mcl-1 with pro-apoptotic protein Bim revealed possible hits with optimal binding energies. All the optimized bicyclic compounds were screened for their in vitro cytotoxic activity against two oral cancer cell lines (AW8507 and AW13516) which express high levels of Bcl-2 and Mcl-1. Compound 4d from the benzimidazole chalcone series and compound 6d from the flavonoid series exhibited significant cytotoxic activity (IC50 7.12 μM and 17.18 μM, respectively) against AW13516 cell line. Time Resolved-Fluorescence Resonance Energy Transfer (TR-FRET) analysis further demonstrated that compound 4d and compound 6d could effectively inhibit the Bcl-2 and Mcl-1 proteins by displacing their BH3 binding partners. Both compounds exhibited potent activation of canonical pathway of apoptosis evident from appearance of cleaved Caspase-3 and PARP. Further, treatment of oral cancer cells with the inhibitors induced dissociation of the BH3 only protein Bim from Mcl-1 and Bak from Bcl-2 but failed to release Bax from Bcl-xL thereby confirming the nature of compounds as BH3-mimetics selectively targeting Bcl-2 and Mcl-1. Our study thus identifies bicyclic compounds as promising candidates for anti-apoptotic Bcl-2/Mcl-1 dual inhibitors with a potential for further development.

  抗凋亡蛋白（如Bcl-2和Mcl-1）的表达升高会导致多种癌症预后不良，并导致对现有治疗方式的耐药性。在此，我们报告了苯并咪唑查尔酮和黄酮类化合物骨架衍生物双环化合物的设计、合成和表征，这些化合物通过优化Bcl-2和Mcl-1结合位点的结构差异，同时靶向这两种蛋白。通过将Bcl-2和Mcl-1与促凋亡蛋白Bim进行初步对接筛选，我们发现了具有最佳结合能的可能的靶向化合物。对所有优化后的双环化合物进行了体外细胞毒性活性筛选，以检测其对两种表达高水平Bcl-2和Mcl-1的口腔癌细胞系（AW8507和AW13516）的细胞毒性活性。苯并咪唑查尔酮系列中的化合物4d和黄酮类化合物系列中的化合物6d对AW13516细胞系表现出显著的细胞毒性活性（IC50分别为7.12 μM和17.18 μM）。时间分辨荧光共振能量转移（TR-FRET）分析进一步表明，化合物4d和化合物6d可通过置换其BH3结合伴侣来有效抑制Bcl-2和Mcl-1蛋白。从裂解的Caspase-3
• Exploring 3-hydroxyflavone scaffolds as mushroom tyrosinase inhibitors: synthesis, X-ray crystallography, antimicrobial, fluorescence behaviour, structure-activity relationship and molecular modelling studies
  作者：Jamshaid Ashraf、Ehsan Ullah Mughal、Amina Sadiq、Maryam Bibi、Nafeesa Naeem、Anser Ali、Anam Massadaq、Nighat Fatima、Asif Javid、Muhammad Naveed Zafar、Bilal Ahmad Khan、Muhammad Faizan Nazar、Amara Mumtaz、Muhammad Nawaz Tahir、Masoud Mirzaei

  DOI：10.1080/07391102.2020.1805364

  日期：2021.12.12

  To explore new scaffolds as tyrosinase enzyme inhibitors remain an interesting goal in the drug discovery and development. In due course and our approach to synthesize bioactive compounds, a series of varyingly substituted 3-hydroxyflavone derivatives (1-23) were synthesized in one-pot reaction and screened forin vitroagainst mushroom tyrosinase enzyme. The structures of newly synthesized compounds were unambiguously corroborated by usual spectroscopic techniques (FTIR, UV-Vis,H-1-,C-13-NMR) and mass spectrometry (EI-MS). The structure of compound15was also characterized by X-ray diffraction analysis. Furthermore, the synthesized compounds (1-23) were evaluated for their antimicrobial potential. Biological studies exhibit pretty good activity against most of the bacterial-fungal strains and their activity is comparable to those of commercially available antibioticsi.e.Cefixime and Clotrimazole. Amongst the series, the compounds2, 4, 5, 6, 7, 10, 11, 14and22exhibited excellent inhibitory activity against tyrosinase, even better than standard compound. Remarkably, the compound2(IC50= 0.280 +/- 0.010 mu g/ml) was found almost sixfold and derivative5(IC50= 0.230 +/- 0.020 mu g/ml) about sevenfold more active as compared to standard Kojic acid (IC50=1.79 +/- 0.6 mu g/ml). Moreover, these synthetic compounds (1-23) displayed good to moderate activities against tested bacterial and fungal strains. Their emission behavior was also investigated in order to know their potential as fluorescent probes. The molecular modelling simulations were also performed to explore their binding interactions with active sites of the tyrosinase enzyme. Limited structure-activity relationship was established to design and develop new tyrosinase inhibitors by employing 2-arylchromone as a structural core in the future. Communicated by Ramaswamy H. Sarma
• Pharmacophore model of the quercetin binding site of the SIRT6 protein
  作者：S. Ravichandran、N. Singh、D. Donnelly、M. Migliore、P. Johnson、C. Fishwick、B.T. Luke、B. Martin、S. Maudsley、S.D. Fugmann、R. Moaddel

  DOI：10.1016/j.jmgm.2014.01.004

  日期：2014.4

  SIRT6 is a histone deacetylase that has been proposed as a potential therapeutic target for metabolic disorders and the prevention of age-associated diseases. We have previously reported on the identification of quercetin and vitexin as SIRT6 inhibitors, and studied structurally related flavonoids including luteolin, kaempferol, apigenin and naringenin. It was determined that the SIRT6 protein remained active after immobilization and that a single frontal displacement could correctly predict the functional activity of the immobilized enzyme. The previous study generated a preliminary pharmacophore for the quercetin binding site on SIRT6, containing 3 hydrogen bond donors and one hydrogen bond acceptor. In this study, we have generated a refined pharmacophore with an additional twelve quercetin analogs. The resulting model had a positive linear behavior between the experimental elution time verses the fit values obtained from the model with a correlation coefficient of 0.8456. Published by Elsevier Inc.
• Synthesis, characterization and cytotoxicity studies of Co(III)-flavonolato complexes
  作者：Máté Kozsup、XueQuan Zhou、Etelka Farkas、Attila Cs. Bényei、Sylvestre Bonnet、Tamás Patonay、Krisztina Kónya、Péter Buglyó

  DOI：10.1016/j.jinorgbio.2021.111382

  日期：2021.4

  with a selective delivery of cytotoxic or antibacterial compounds. Whithin this field sixteen novel Co(III) ternary complexes with the general formula [Co(4N)(flav)](ClO4)2, where 4N = tris(2-aminoethyl)amine (tren) or tris(2-pyridylmethyl)amine (tpa) and flav = deprotonated form of differently substituted flavonols have been synthesized, characterized, and their cytotoxicity assayed under both normoxic

  作为前药的缺氧活化的 Co(III) 复合物可以提供细胞毒性或抗菌化合物的选择性递送。在该领域内有十六种新型 Co(III) 三元配合物，通式为 [Co(4N)(flav)](ClO 4 ) 2, 其中 4N = 三 (2-氨基乙基) 胺 (tren) 或三 (2-吡啶基甲基) 胺 (tpa) 和 flav = 不同取代的黄酮醇的去质子化形式已被合成、表征并在常氧和缺氧条件下测定其细胞毒性. 还报道了两种游离黄酮醇和七种配合物的分子结构。在所有配合物中，生物配体表现出预期的 (O,O) 配位模式，并且配合物表现出略微扭曲的八面体几何形状。循环伏安研究表明，黄酮醇的取代基和 4N 供体配体的类型对复合物的还原电位都有影响。含有tren的那些表现出比tpa类似物显着更高的稳定性，使这些以前的化合物成为开发缺氧激活的前药复合物的有希望的候选者。Tpa 复合物对两种选定的人类癌细胞系（A549、A