neolamellarin A | 959860-11-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: neolamellarin A
• 英文别名: 1-(3,4-bis(4-hydroxyphenyl)-1H-pyrrol-1-yl)-2-(4-hydroxyphenyl)ethan-1-one；1-[3,4-bis(4-hydroxyphenyl)pyrrol-1-yl]-2-(4-hydroxyphenyl)ethanone
• CAS: 959860-11-8
• 化学式: C₂₄H₁₉NO₄
• 分子量: 385.419
• InChiKey: ANCFAUCOYOMNJZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  82.7
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (3,4-bis(4-methoxyphenyl)pyrrole-1-yl)-2-(4-methoxyphenyl)ethanone 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 以49%的产率得到neolamellarin A
  参考文献：
  名称：

  Structure-activity relationships study of neolamellarin A and its analogues as hypoxia inducible factor-1 (HIF-1) inhibitors

  摘要：

  The novel marine pyrrole alkaloid neolamellarin A derived from sponge has been shown to inhibit hypoxia-induced HIF-1 activity. In this work, we designed and synthesized neolamellarin A and its series of derivatives by a convergent synthetic strategy. The HIF-1 inhibitory activity and cytotoxicity of these compounds were evaluated in Hela cells by dual-luciferase reporter gene assay and MIT assay, respectively. The results showed that neolamellarin A 1 (IC50 = 10.8 +/- 1.0 mu M) and derivative 2b (IC50 = 11.9 +/- 3.6 mu M) had the best HIF-1 inhibitory activity and low cytotoxicity. Our SAR research focused on the effects of key regions aliphatic carbon chain length, aromatic ring substituents and C-7 substituent on biological activity, providing a basis for the subsequent research on the development of novel pyrrole alkaloids as HIF-1 inhibitors and design of small molecule probes for target protein identification.

  DOI：

  10.1016/j.bmcl.2019.06.017

文献信息

• Structure-activity relationships study of neolamellarin A and its analogues as hypoxia inducible factor-1 (HIF-1) inhibitors
  作者：Guangzhe Li、Huijuan Dong、Yao Ma、Kun Shao、Yueqing Li、Xiaodan Wu、Shisheng Wang、Yujie Shao、Weijie Zhao

  DOI：10.1016/j.bmcl.2019.06.017

  日期：2019.8

  The novel marine pyrrole alkaloid neolamellarin A derived from sponge has been shown to inhibit hypoxia-induced HIF-1 activity. In this work, we designed and synthesized neolamellarin A and its series of derivatives by a convergent synthetic strategy. The HIF-1 inhibitory activity and cytotoxicity of these compounds were evaluated in Hela cells by dual-luciferase reporter gene assay and MIT assay, respectively. The results showed that neolamellarin A 1 (IC50 = 10.8 +/- 1.0 mu M) and derivative 2b (IC50 = 11.9 +/- 3.6 mu M) had the best HIF-1 inhibitory activity and low cytotoxicity. Our SAR research focused on the effects of key regions aliphatic carbon chain length, aromatic ring substituents and C-7 substituent on biological activity, providing a basis for the subsequent research on the development of novel pyrrole alkaloids as HIF-1 inhibitors and design of small molecule probes for target protein identification.