(E)-2-(3,4-dihydroxybenzyliden)-2,3-dihydro-1H-inden-1-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: (E)-2-(3,4-dihydroxybenzyliden)-2,3-dihydro-1H-inden-1-one
• 英文别名: 2-(3,4-dihydroxybenzylidene)-2,3-dihydro-1H-inden-1-one；2-((3,4-Dihydroxyphenyl)methylene)indan-1-one；(2E)-2-[(3,4-dihydroxyphenyl)methylidene]-3H-inden-1-one
• 化学式: C₁₆H₁₂O₃
• 分子量: 252.269
• InChiKey: PPOMQCAGVJQMEO-KPKJPENVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3,4-二(四氢吡喃-2-氧基)苯甲醛 在 barium hydroxide octahydrate 、 对甲苯磺酸 作用下， 以 甲醇 为溶剂， 反应 18.0h， 生成 (E)-2-(3,4-dihydroxybenzyliden)-2,3-dihydro-1H-inden-1-one
  参考文献：
  名称：

  Geometrically and Conformationally Restrained Cinnamoyl Compounds as Inhibitors of HIV-1 Integrase:  Synthesis, Biological Evaluation, and Molecular Modeling

  摘要：

  Various cinnammoyl-based structures were synthesized and tested in enzyme assays as inhibitors of the HIV-1 integrase (IN). The majority of compounds were designed as geometrically or conformationally constrained analogues of caffeic acid phenethyl ester (CAPE) and were characterized by a syn disposition of the carbonyl group with respect to the vinylic double bond. Since the cinnamoyl moiety present in flavones such as quercetin (inactive on HIV-1-infected cells) is frozen in an anti arrangement, it was hoped that fixing our compounds in a syn disposition could favor anti-HIV-1 activity in cell-based assays. Geometrical and conformational properties of the designed compounds were taken into account through analysis of X-ray structures available from the Cambridge Structural Database. The polyhydroxylated analogues were prepared by reacting 3,4-bis(tetrahydropyran-2-yloxy)benzaldehyde with various compounds having active methylene groups such as 2-propanone, cyclopentanone, cyclohexanone, 1,3-diacetylbenzene, 2,4-dihydroxyacetophenone, 2,3-dihydro-1-indanone, 2,3-dihydro-1,3-indandione, and others. While active against both 3'-processing and strand-transfer reactions, the new compounds, curcumin included, failed to inhibit the HIV-1 multiplication in acutely infected MT-4 cells. Nevertheless, they specifically inhibited the enzymatic reactions associated with IN, being totally inactive against other viral (HIV-1 reverse transcriptase) and cellular (RNA polymerase II) nucleic acid-processing enzymes. On the other hand, title compounds were endowed with remarkable antiproliferative activity, whose potency correlated neither with the presence of catechols (possible source of reactive quinones) nor with inhibition of topoisomerases. The SARs developed for our compounds led to novel findings concerning the molecular determinants of IN inhibitory activity within the class of cinnamoyl-based structures. We hypothesize that these compounds bind to IN featuring the cinnamoyl residue C=C-C=O in a syn disposition, differently from flavone derivatives characterized by an anti arrangement about the same fragment. Certain inhibitors, lacking one of the two pharmacophoric catechol hydroxyls, retain moderate potency thanks to nonpharmacophoric fragments (i.e., a m-methoxy group in curcumin) which favorably interact with an "accessory" region of IN. This region is supposed to be located adjacent to the binding site accommodating the pharmacophoric dihydroxycinnamoyl moiety. Disruption of coplanarity in the inhibitor structure abolishes activity owing to poor shape complementarity with the target or an exceedingly high strain energy of the coplanar conformation.

  DOI：

  10.1021/jm9707232

文献信息

• Discovery of benzofuran-3(2 H )-one derivatives as novel DRAK2 inhibitors that protect islet β-cells from apoptosis
  作者：Sheng Wang、Lei Xu、Yu-Ting Lu、Yu-Fei Liu、Bing Han、Ting Liu、Jie Tang、Jia Li、Jiangping Wu、Jing-Ya Li、Li-Fang Yu、Fan Yang

  DOI：10.1016/j.ejmech.2017.02.048

  日期：2017.4

  kinase-related apoptosis-inducing kinase-2 (DRAK2) is a serine/threonine kinase that plays a key role in a wide variety of cell death signaling pathways. Inhibition of DRAK2 was found to efficiently protect islet β-cells from apoptosis and hence DRAK2 inhibitors represent a promising therapeutic strategy for the treatment of diabetes. Only very few chemical entities targeting DRAK2 are currently known. We carried

  死亡相关的蛋白激酶相关的凋亡诱导激酶2（DRAK2）是一种丝氨酸/苏氨酸激酶，在多种细胞死亡信号传导途径中起关键作用。发现抑制DRAK2可有效保护胰岛β细胞免于凋亡，因此DRAK2抑制剂代表了治疗糖尿病的有前途的治疗策略。目前仅知道靶向DRAK2的化学实体很少。我们进行了高通量筛选，并将化合物4鉴定为中度DRAK2抑制剂，IC50值为3.15μM。随后对命中化合物4的SAR研究导致开发出新型的benzofuRAn-3（2H）-DRAK2抑制剂系列，具有针对26种所选激酶的增强的效能和有利的选择性。重要的是，大多数有效化合物40（IC50 = 0.33μM）和41（IC50 = 0。发现25μM）以剂量依赖性方式保护胰岛β细胞免于凋亡。这些数据支持以下观点：DRAK2的小分子抑制剂代表了治疗糖尿病的有前途的策略。
• In vitro and in silico insights into tyrosinase inhibitors with (E)-benzylidene-1-indanone derivatives
  作者：Hee Jin Jung、Sang Gyun Noh、Yujin Park、Dongwan Kang、Pusoon Chun、Hae Young Chung、Hyung Ryong Moon

  DOI：10.1016/j.csbj.2019.07.017

  日期：——

  Tyrosinase is a key enzyme responsible for melanin biosynthesis and is effective in protecting skin damage caused by ultraviolet radiation. As part of ongoing efforts to discover potent tyrosinase inhibitors, we systematically designed and synthesized thirteen (E)-benzylidene-l-indanone derivatives (BID1-13) and determined their inhibitory activities against tyrosinase. Among the compounds evaluated, BID3 was the most potent inhibitor of mushroom tyrosinase (IC50 = 0.034 mu M, monophenolase activity; IC50 = 1.39 mu M, diphenolase activity). Kinetic studies revealed that BID3 demonstrated a mixed type of tyrosinase inhibition with K-i value of 2.4 mu M using L-DOPA as a substrate. In silico molecular docking simulations demonstrated that BID3 can bind to the catalytic and allosteric sites of tyrosinase to inhibit enzyme activity which confirmed in vitro experimental studies between BID3 and tyrosinase. Furthermore, melanin contents decreased and cellular tyrosinase activity was inhibited after BID3 treatment. These observations revealed that BID3 is a potent tyrosinase inhibitor and potentially could be used as a whitening agent for the treatment of pigmentation-related disorders. (C) 2019 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.