7-(N-[(phenylsulfonyl)piperazinyl]methyl)-(20S)-camptothecin

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 喜树碱
• 英文名称: 7-(N-[(phenylsulfonyl)piperazinyl]methyl)-(20S)-camptothecin
• 英文别名: (19S)-10-[[4-(benzenesulfonyl)piperazin-1-yl]methyl]-19-ethyl-19-hydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15(20)-heptaene-14,18-dione
• 化学式: C₃₁H₃₀N₄O₆S
• 分子量: 586.668
• InChiKey: KIPUREBAFAJFCX-HKBQPEDESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  42
• 可旋转键数：
  5
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  129
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  7-hydroxymethylcamptothecin 在 硫酸 、 氢溴酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 28.0h， 生成 7-(N-[(phenylsulfonyl)piperazinyl]methyl)-(20S)-camptothecin
  参考文献：
  名称：

  Design, synthesis and potent cytotoxic activity of novel 7-( N -[(substituted-sulfonyl)piperazinyl]-methyl)-camptothecin derivatives

  摘要：

  In an effort to discover potent camptothecin-derived antitumor agents, novel camptothecin analogues with sulfonylpiperazinyl motifs at position-7 were designed and synthesized. They were evaluated for in vitro cytotoxicity with the sulforhodamine-B (SRB) method in five types of human tumor cell lines, A-549, MDA-MB-231, KB, KB-VIN and MCF-7. With IC50 values in the low mu M to nM level, most of the new analogues showed greater cytotoxicity activity than the reference compounds irinotecan and topotecan. Furthermore, compounds 121 (IC50, 1.2 nM) and 12k (IC50, 20.2 nM) displayed the highest cytotoxicity against the multidrug-resistant (MDR) KB-VIN cell line and merit further development as preclinical drug candidates for treating cancer, including MDR phenotype. Our study suggested that integration of sulfonylpiperazinyl motifs into position-7 of camptothecin is an effective strategy for discovering new potent cytotoxic camptothecin derivatives. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.02.066

文献信息

• Design, synthesis and potent cytotoxic activity of novel 7-( N -[(substituted-sulfonyl)piperazinyl]-methyl)-camptothecin derivatives
  作者：Gao-Xiang Zhu、Pi-Le Cheng、Masuo Goto、Na Zhang、Susan L. Morris-Natschke、Kan-Yen Hsieh、Guan-Zhou Yang、Qian-Ru Yang、Ying-Qian Liu、Hai-Le Chen、Xiao-Shuai Zhang、Kuo-Hsiung Lee

  DOI：10.1016/j.bmcl.2017.02.066

  日期：2017.4

  In an effort to discover potent camptothecin-derived antitumor agents, novel camptothecin analogues with sulfonylpiperazinyl motifs at position-7 were designed and synthesized. They were evaluated for in vitro cytotoxicity with the sulforhodamine-B (SRB) method in five types of human tumor cell lines, A-549, MDA-MB-231, KB, KB-VIN and MCF-7. With IC50 values in the low mu M to nM level, most of the new analogues showed greater cytotoxicity activity than the reference compounds irinotecan and topotecan. Furthermore, compounds 121 (IC50, 1.2 nM) and 12k (IC50, 20.2 nM) displayed the highest cytotoxicity against the multidrug-resistant (MDR) KB-VIN cell line and merit further development as preclinical drug candidates for treating cancer, including MDR phenotype. Our study suggested that integration of sulfonylpiperazinyl motifs into position-7 of camptothecin is an effective strategy for discovering new potent cytotoxic camptothecin derivatives. (C) 2017 Elsevier Ltd. All rights reserved.