2'-hydroxy-2,5'-dimethoxychalcone

• 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: 2'-hydroxy-2,5'-dimethoxychalcone
• 英文别名: 1-(2-Hydroxy-5-methoxyphenyl)-3-(2-methoxyphenyl)prop-2-en-1-one
• 化学式: C₁₇H₁₆O₄
• 分子量: 284.312
• InChiKey: XYLTVAMWWGAIFM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2'-hydroxy-2,5'-dimethoxychalcone 在 disodium hydrogenphosphate 作用下， 以 乙醇 、 水 为溶剂， 反应 36.0h， 以84%的产率得到6,2'-dimethoxyflavanone
  参考文献：
  名称：

  5′-Chloro-2,2′-dihydroxychalcone and related flavanoids as treatments for prostate cancer

  摘要：

  Several flavonoids and their biosynthetic precursor chalcones were designed and synthesized to improve the biological effects of the lead compound 2'-hydroxyflavonone against androgen receptor (AR)-dependent transcriptional stimulation. Newly synthesized chalcones 19 and 26 suppressed AR dependent transcription as well as DHT-dependent growth stimulation at a low micromolar level. These compounds were also effective against ligand-independent constitutively active mutant AR derived from castration-resistant PCa (CRPC). Compounds 19 and 26 showed broad spectrum anti-proliferative activity at 5-10 mu M against multiple tumor cell lines including androgen-independent and taxane-resistant prostate cancer as well as a multidrug-resistant subline. Mode of action studies suggested that 19 induced sub-G1 accumulation in PC-3 cells by disrupting the microtubule network without affecting cell cycle progression. Furthermore, the in vivo effectiveness of chalcone 19 was confirmed in a xenograft model antitumor assay. Thus, chalcone 19 has the potential to be a bifunctional lead for treatment of AR-dependent PCa at lower doses as well as AR-independent PCa, including CRPC, at higher doses. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.08.069
• 作为产物：
  描述：

  水杨醛 在 potassium hydroxide 、 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 8.5h， 生成 2'-hydroxy-2,5'-dimethoxychalcone
  参考文献：
  名称：

  5′-Chloro-2,2′-dihydroxychalcone and related flavanoids as treatments for prostate cancer

  摘要：

  Several flavonoids and their biosynthetic precursor chalcones were designed and synthesized to improve the biological effects of the lead compound 2'-hydroxyflavonone against androgen receptor (AR)-dependent transcriptional stimulation. Newly synthesized chalcones 19 and 26 suppressed AR dependent transcription as well as DHT-dependent growth stimulation at a low micromolar level. These compounds were also effective against ligand-independent constitutively active mutant AR derived from castration-resistant PCa (CRPC). Compounds 19 and 26 showed broad spectrum anti-proliferative activity at 5-10 mu M against multiple tumor cell lines including androgen-independent and taxane-resistant prostate cancer as well as a multidrug-resistant subline. Mode of action studies suggested that 19 induced sub-G1 accumulation in PC-3 cells by disrupting the microtubule network without affecting cell cycle progression. Furthermore, the in vivo effectiveness of chalcone 19 was confirmed in a xenograft model antitumor assay. Thus, chalcone 19 has the potential to be a bifunctional lead for treatment of AR-dependent PCa at lower doses as well as AR-independent PCa, including CRPC, at higher doses. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.08.069

文献信息

• Synthesis, characterization and biological evaluation of pyrazole-based benzene sulfonamides as inhibitors of human carbonic anhydrase II, IX and XII
  作者：Tajamul Hussain、Saif Ullah、Salman Alrokayan、Salman Alamery、Arif Ahmed Mohammed、Syeda Abida Ejaz、Mubashir Aziz、Jamshed Iqbal

  DOI：10.1039/d3ra03276k

  日期：——

  The aberrant level of the carbonic anhydrase isozymes is linked with various disorders which include glaucoma, epilepsy, altitude sickness and obesity. In the present study, a series of the pyrazole-based benzene sulfonamides derivatives (4a–4l) were designed, synthesized and evaluated as the inhibitors of the three isoforms of human carbonic anhydrases (hCAII, hCAIX and hCAXII). A number of the derivatives

  碳酸酐酶同工酶的异常水平与多种疾病有关，包括青光眼、癫痫、高原反应和肥胖。在本研究中，设计、合成了一系列基于吡唑的苯磺酰胺衍生物（4a-4l ），并对其作为人碳酸酐酶三种亚型（hCAII、hCAIX和hCAXII）的抑制剂进行了评估。发现许多衍生物比用作人 hCAII、hCAIX 和 hCAXII 标准品的乙酰唑酰胺更具活性。该系列中，化合物4k将hCAII抑制至亚微摩尔水平，IC 50 ± SEM浓度为0.24 ± 0.18 μM，抑制剂4j将hCAIX的活性降低至IC 50± SEM 等于 0.15 ± 0.07 μM，而分子4g在 IC 50浓度低至0.12 ± 0.07 μM 时就阻断了同工酶 hCAXII 的催化潜力。此外，与 hCAIX 和 hCAXII 相比，化合物 4e 和 4k 被筛选为异构体 hCAXII 的优先抑制剂，最大浓度的一半分别为 0.75 ± 0.13 μM
• 5′-Chloro-2,2′-dihydroxychalcone and related flavanoids as treatments for prostate cancer
  作者：Yohei Saito、Atsushi Mizokami、Hiroyuki Tsurimoto、Kouji Izumi、Masuo Goto、Kyoko Nakagawa-Goto

  DOI：10.1016/j.ejmech.2018.08.069

  日期：2018.9

  Several flavonoids and their biosynthetic precursor chalcones were designed and synthesized to improve the biological effects of the lead compound 2'-hydroxyflavonone against androgen receptor (AR)-dependent transcriptional stimulation. Newly synthesized chalcones 19 and 26 suppressed AR dependent transcription as well as DHT-dependent growth stimulation at a low micromolar level. These compounds were also effective against ligand-independent constitutively active mutant AR derived from castration-resistant PCa (CRPC). Compounds 19 and 26 showed broad spectrum anti-proliferative activity at 5-10 mu M against multiple tumor cell lines including androgen-independent and taxane-resistant prostate cancer as well as a multidrug-resistant subline. Mode of action studies suggested that 19 induced sub-G1 accumulation in PC-3 cells by disrupting the microtubule network without affecting cell cycle progression. Furthermore, the in vivo effectiveness of chalcone 19 was confirmed in a xenograft model antitumor assay. Thus, chalcone 19 has the potential to be a bifunctional lead for treatment of AR-dependent PCa at lower doses as well as AR-independent PCa, including CRPC, at higher doses. (C) 2018 Elsevier Masson SAS. All rights reserved.