N-(6-fluorobenzo[d]thiazol-2-yl)-1,3-diphenyl-1H-pyrazole-4-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-(6-fluorobenzo[d]thiazol-2-yl)-1,3-diphenyl-1H-pyrazole-4-carboxamide
• 英文别名: N-(6-fluoro-1,3-benzothiazol-2-yl)-1,3-diphenylpyrazole-4-carboxamide
• 化学式: C₂₃H₁₅FN₄OS
• 分子量: 414.463
• InChiKey: BCGLFSYECNRIGQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  88
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1,3-二苯-1H-吡唑-4-甲醛 在 sodium chlorite 、 氨基磺酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 17.17h， 生成 N-(6-fluorobenzo[d]thiazol-2-yl)-1,3-diphenyl-1H-pyrazole-4-carboxamide
  参考文献：
  名称：

  Pyrazolo-benzothiazole hybrids: Synthesis, anticancer properties and evaluation of antiangiogenic activity using in vitro VEGFR-2 kinase and in vivo transgenic zebrafish model

  摘要：

  A series of new pyrazolo-benzothiazole hybrids (7-26) were synthesised and screened for their cytotoxic activity towards several cancer cell lines [colon (HT-29), prostate (PC-3), lung (A549), glioblastoma (U87MG)] and normal human embryonic kidney cell line (Hek-293T). Compounds 8, 9, 13, 14, 18, 19, 23, and 24 displayed significant activity, with compound 14 being particularly potent towards all the tested cancer cell lines with IC50 values in the range 3.17-6.77 mu M, even better than reference drug axitinib (4.88-21.7 mu M). Compound 14 also showed the strongest growth inhibition in 3D multicellular spheroids of PC-3 and U87MG cells. The mechanism of cellular toxicity in PC-3 cells was found to be cell cycle arrest and apoptosis induction through depolarisation of mitochondrial membrane potential, increased ROS production and subsequent DNA damage. Further, compound 14 displayed significant in vitro (VEGFR-2 inhibition) and in vivo [transgenic zebrafish Tg(flila:EGFP) model] antiangiogenic properties. Overall, these results provide strong evidence that compound 14 could be considered for a lead candidate in anticancer and antiangiogenic drug discovery. (C) 2019 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2019.111609

文献信息

• Pyrazolo-benzothiazole hybrids: Synthesis, anticancer properties and evaluation of antiangiogenic activity using in vitro VEGFR-2 kinase and in vivo transgenic zebrafish model
  作者：Velma Ganga Reddy、T. Srinivasa Reddy、Chetna Jadala、M. Soumya Reddy、Faria Sultana、Ravikumar Akunuri、Suresh K. Bhargava、Donald Wlodkowic、P. Srihari、Ahmed Kamal

  DOI：10.1016/j.ejmech.2019.111609

  日期：2019.11

  A series of new pyrazolo-benzothiazole hybrids (7-26) were synthesised and screened for their cytotoxic activity towards several cancer cell lines [colon (HT-29), prostate (PC-3), lung (A549), glioblastoma (U87MG)] and normal human embryonic kidney cell line (Hek-293T). Compounds 8, 9, 13, 14, 18, 19, 23, and 24 displayed significant activity, with compound 14 being particularly potent towards all the tested cancer cell lines with IC50 values in the range 3.17-6.77 mu M, even better than reference drug axitinib (4.88-21.7 mu M). Compound 14 also showed the strongest growth inhibition in 3D multicellular spheroids of PC-3 and U87MG cells. The mechanism of cellular toxicity in PC-3 cells was found to be cell cycle arrest and apoptosis induction through depolarisation of mitochondrial membrane potential, increased ROS production and subsequent DNA damage. Further, compound 14 displayed significant in vitro (VEGFR-2 inhibition) and in vivo [transgenic zebrafish Tg(flila:EGFP) model] antiangiogenic properties. Overall, these results provide strong evidence that compound 14 could be considered for a lead candidate in anticancer and antiangiogenic drug discovery. (C) 2019 Published by Elsevier Masson SAS.