4-benzoyl-1-[(naphth-1-yl)acetyl]thiosemicarbazide

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 4-benzoyl-1-[(naphth-1-yl)acetyl]thiosemicarbazide
• 英文别名: N-[[(2-naphthalen-1-ylacetyl)amino]carbamothioyl]benzamide
• 化学式: C₂₀H₁₇N₃O₂S
• 分子量: 363.44
• InChiKey: AXRMQGOMBGMRTH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  102
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1-萘乙酰肼 、 苯甲酰基异硫氰酸酯 以 乙醇 为溶剂， 以86 %的产率得到4-benzoyl-1-[(naphth-1-yl)acetyl]thiosemicarbazide
  参考文献：
  名称：

  Identification of the first-in-class dual inhibitors of human DNA topoisomerase IIα and indoleamine-2,3-dioxygenase 1 (IDO 1) with strong anticancer properties

  摘要：

  Molecular docking of a large set of thiosemicarbazide-based ligands resulted in obtaining compounds that inhibited both human DNA topoisomerase IIα and indoleamine-2,3-dioxygenase-1 (IDO1). To the best of our knowledge, these compounds are the first dual inhibitors targeting these two enzymes. As both of them participate in the anticancer response, the effect of the compounds on a panel of cancer cell lines was examined. Among the cell lines tested, lung cancer (A549) and melanoma (A375) cells were the most sensitive to compounds 1 (IC50=0.23 µg/ml), 2 (IC50=0.83 µg/ml) and 3 (IC50=0.25 µg/ml). The observed activity was even 90-fold higher than that of etoposide, with selectivity index values reaching 125. In-silico simulations showed that contact between 1-3 and human DNA topoisomerase II was maintained through aromatic moieties located at limiting edges of ligand molecules and intensive interactions of the thiosemicarbazide core with the DNA fragments present in the catalytic site of the enzyme.

  DOI：

  10.1080/14756366.2022.2140420

文献信息

• Identification of the first-in-class dual inhibitors of human DNA topoisomerase IIα and indoleamine-2,3-dioxygenase 1 (IDO 1) with strong anticancer properties
  作者：Barbara Kaproń、Anita Płazińska、Wojciech Płaziński、Tomasz Plech

  DOI：10.1080/14756366.2022.2140420

  日期：2023.1.1

  Molecular docking of a large set of thiosemicarbazide-based ligands resulted in obtaining compounds that inhibited both human DNA topoisomerase IIα and indoleamine-2,3-dioxygenase-1 (IDO1). To the best of our knowledge, these compounds are the first dual inhibitors targeting these two enzymes. As both of them participate in the anticancer response, the effect of the compounds on a panel of cancer cell lines was examined. Among the cell lines tested, lung cancer (A549) and melanoma (A375) cells were the most sensitive to compounds 1 (IC50=0.23 µg/ml), 2 (IC50=0.83 µg/ml) and 3 (IC50=0.25 µg/ml). The observed activity was even 90-fold higher than that of etoposide, with selectivity index values reaching 125. In-silico simulations showed that contact between 1-3 and human DNA topoisomerase II was maintained through aromatic moieties located at limiting edges of ligand molecules and intensive interactions of the thiosemicarbazide core with the DNA fragments present in the catalytic site of the enzyme.