(2Z,5Z)-3-(3-(3-(diethylamino)propyl)-5-(3,4,5-trimethoxybenzylidene)-4-oxo-2-thiazolidinylidene)-5-methylindolin-2-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (2Z,5Z)-3-(3-(3-(diethylamino)propyl)-5-(3,4,5-trimethoxybenzylidene)-4-oxo-2-thiazolidinylidene)-5-methylindolin-2-one
• 英文别名: (2Z,5Z)-3-[3-(diethylamino)propyl]-2-(5-methyl-2-oxo-1H-indol-3-ylidene)-5-[(3,4,5-trimethoxyphenyl)methylidene]-1,3-thiazolidin-4-one
• 化学式: C₂₉H₃₅N₃O₅S
• 分子量: 537.68
• InChiKey: AKXDFTZIFCOQRI-BMLDQOIQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  38
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-(3-(diethylamino)propyl)-2-thioxothiazolidin-4-one 在 哌啶 、 三氟化硼乙醚 、 三乙胺 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 反应 8.0h， 生成 (2Z,5Z)-3-(3-(3-(diethylamino)propyl)-5-(3,4,5-trimethoxybenzylidene)-4-oxo-2-thiazolidinylidene)-5-methylindolin-2-one 、 (2E,5Z)-3-(3-(3-(diethylamino)propyl)-5-(3,4,5-trimethoxybenzylidene)-4-oxo-2-thiazolidinylidene)-5-methylindolin-2-one
  参考文献：
  名称：

  Design, synthesis and biological evaluation of novel 4-thiazolidinones containing indolin-2-one moiety as potential antitumor agent

  摘要：

  A series of novel 4-thiazolidinone and indolin-2-one hybrid derivatives 5a-5s and 10a-10s have been designed and synthesized and their cytotoxic activities were evaluated in vitro against three human cancer cell lines including HT-29 (human colon cancer), H460 (human lung cancer), MDA-MB-231 (human breast cancer) by MTT assay. Several potent target compounds (5m, 5p, 5s, 10a, 10c-10g, 10m, 10p) were further evaluated against one cancer cell line SMMC-7721 (human liver cancer) and one normal cell line WI-38 (human fetal lung fibroblasts). Most of the prepared compounds exhibited significant antitumor activities against different human cancer cell lines. Compound 10c (IC50 = 0.025 mu M. 0.075 mu M, 0.77 mu M, 1.95 mu M) was 52, 36, 4.8 and 3.3 times more active than Sunitinib (IC50 = 1.3 mu M, 2.7 mu M, 3.7 mu M, 6.47 mu M) against HT-29, H460, MDA-MB-231 and SMMC-7721 cancer cell line, respectively. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.05.017

文献信息

• The interaction of 4-thiazolidinone derivatives containing indolin-2-one moiety with P-glycoprotein studied using K562 cell lines
  作者：Feng Wang、Zijian Liu、Jian Wang、Jun Tao、Ping Gong、Xue Bao、Yanfang Zhao、Yulin Wang

  DOI：10.1016/j.ejmech.2015.06.002

  日期：2015.8

  P-glycoprotein (P-gp) is an active drug efflux pump, which exists widely in various MDR tumor cells, conferring drug resistance to tumor cells during chemotherapy. Some 4-thiazolidinone derivatives containing indolin-2-one moiety are novel anti-tumor compounds. The aim of this study was to evaluate the transport activity of P-gp towards 4-thiazolidinone derivatives containing indolin-2-one moiety (as mixtures of 2Z, 5Z and 2E, 5Z isomers) and the transport inhibition activities of the derivatives to P-gp, the results of which could provide crucial information for the further separation of and development on the derivatives with excellent anti-tumor activities. The results indicate that the further separation and development should be focused on compounds 7, 10, 12 and 13 (tumor cell cytotoxic P-gp modulators) and compounds 8, 9, 17 and 18 (non-substrates of P-gp), which exhibit anti-tumor activities and could overcome P-gp mediated MDR. Furthermore, the results of molecular docking indicate that Ser222, a residue in TM4 domain of P-gp, exhibits an intriguing feature in that it interacts with all of the derivatives related with P-gp transport in a significant way, including both typical substrates and modulators of P-gp. Meanwhile, the compounds showing no interaction with Ser222 are mainly from the category of non-substrates of P-gp. Therefore, the interaction between Ser222 and the tested derivative would provide useful information for the further development on 4-thiazolidinone derivatives containing indolin-2-one moiety. (C) 2015 Elsevier Masson SAS. All rights reserved.