Tert-butyl 2-(5-hydroxy-4-oxo-2-phenylchromen-7-yl)oxyacetate

• 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: Tert-butyl 2-(5-hydroxy-4-oxo-2-phenylchromen-7-yl)oxyacetate
• 化学式: C₂₁H₂₀O₆
• mdl: MFCD02081664
• 分子量: 368.386
• InChiKey: TWBYICCJKQMSBJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  82.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Tert-butyl 2-(5-hydroxy-4-oxo-2-phenylchromen-7-yl)oxyacetate 在 三氟乙酸 作用下， 反应 2.0h， 以88.7%的产率得到2-(5-羟基-4-氧代-2-苯基-4H-色烯-7-基氧基)乙酸
  参考文献：
  名称：

  Inhibiting epidermal growth factor receptor signalling potentiates mesenchymal–epithelial transition of breast cancer stem cells and their responsiveness to anticancer drugs

  摘要：

  The recurrence of breast cancer in patients is a persistent challenge to the medical fraternity. Breast tumor contains a small population of cells with high tumor initiating and metastatic potential, known as cancer stem cells (CSCs), which are resistant to existing chemotherapeutics. CSCs contribute to the aggressiveness of triple negative breast cancers (TNBCs), thereby necessitating the identification of molecular targets on breast CSCs. TNBC cell line MDA‐MB‐231, in comparison with MCF‐7, demonstrated a higher expression of epidermal growth factor receptor (EGFR). Thus, the naturally occurring flavanone, chrysin, with limited potential as a chemotherapeutic agent, was structurally modified by designing an analog with EGFR binding affinity using a molecular docking approach and subsequently synthesised. Chrysin analog CHM‐09 and known EGFR inhibitors demonstrated a comparable anti‐proliferative, anti‐migratory activity along with the induction of apoptosis and cell cycle arrest in MDA‐MB‐231. Furthermore, sorted CD24−/CD44+‐breast CSCs and CD24+‐breast cancer cells from MDA‐MB‐231 demonstrated a markedly high expression of EGFR in the former than in the latter. CHM‐09 and EGFR inhibitors could perturb EGF‐induced EGFR signalling of breast CSC proliferation, migration, mammosphere formation and mesenchymal tri‐lineage differentiation. CHM‐09 or EGFR inhibitors not only led to inactivation of EGFR downstream signalling pathways such as Akt, extracellular signal regulated kinase and signal transducer and activator of transcription 3, but also induction of mesenchymal–epithelial transition as confirmed by decreased N‐cadherin and increased E‐cadherin expression. Finally, combinatorial treatment of EGFR inhibitors and doxorubicin led to significant increase in breast CSCs responsiveness to a chemotherapeutic drug. The results of the present study suggest that EGFR is a therapeutic target in breast CSCs and that abrogation of EGFR signalling along with chemotherapeutic drugs is an effective approach against breast cancer.

  DOI：

  10.1111/febs.14084
• 作为产物：
  描述：

  溴乙酸叔丁酯 、 白杨素 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 3.0h， 以86%的产率得到Tert-butyl 2-(5-hydroxy-4-oxo-2-phenylchromen-7-yl)oxyacetate
  参考文献：
  名称：

  Inhibiting epidermal growth factor receptor signalling potentiates mesenchymal–epithelial transition of breast cancer stem cells and their responsiveness to anticancer drugs

  摘要：

  The recurrence of breast cancer in patients is a persistent challenge to the medical fraternity. Breast tumor contains a small population of cells with high tumor initiating and metastatic potential, known as cancer stem cells (CSCs), which are resistant to existing chemotherapeutics. CSCs contribute to the aggressiveness of triple negative breast cancers (TNBCs), thereby necessitating the identification of molecular targets on breast CSCs. TNBC cell line MDA‐MB‐231, in comparison with MCF‐7, demonstrated a higher expression of epidermal growth factor receptor (EGFR). Thus, the naturally occurring flavanone, chrysin, with limited potential as a chemotherapeutic agent, was structurally modified by designing an analog with EGFR binding affinity using a molecular docking approach and subsequently synthesised. Chrysin analog CHM‐09 and known EGFR inhibitors demonstrated a comparable anti‐proliferative, anti‐migratory activity along with the induction of apoptosis and cell cycle arrest in MDA‐MB‐231. Furthermore, sorted CD24−/CD44+‐breast CSCs and CD24+‐breast cancer cells from MDA‐MB‐231 demonstrated a markedly high expression of EGFR in the former than in the latter. CHM‐09 and EGFR inhibitors could perturb EGF‐induced EGFR signalling of breast CSC proliferation, migration, mammosphere formation and mesenchymal tri‐lineage differentiation. CHM‐09 or EGFR inhibitors not only led to inactivation of EGFR downstream signalling pathways such as Akt, extracellular signal regulated kinase and signal transducer and activator of transcription 3, but also induction of mesenchymal–epithelial transition as confirmed by decreased N‐cadherin and increased E‐cadherin expression. Finally, combinatorial treatment of EGFR inhibitors and doxorubicin led to significant increase in breast CSCs responsiveness to a chemotherapeutic drug. The results of the present study suggest that EGFR is a therapeutic target in breast CSCs and that abrogation of EGFR signalling along with chemotherapeutic drugs is an effective approach against breast cancer.

  DOI：

  10.1111/febs.14084