新型2-杂芳基亚氨基-1,3-噻唑烷-4-酮作为潜在抗肿瘤药物的合成及生物学评价
Synthesis and biological evaluation of novel 2-heteroarylimino-1,3-thiazolidin-4-ones as potential anti-tumor agents.
作者信息
Revelant Germain, Huber-Villaume Sophie, Dunand Sandrine, Kirsch Gilbert, Schohn Hervé, Hesse Stéphanie
机构信息
Université de Lorraine, UMR CNRS 7565, Structure et Réactivité des Systèmes Moléculaires Complexes - Equipe 3 (HECRIN), 1 Boulevard Arago, 57070 Metz Technopôle, France.
Université de Lorraine, UMR CNRS 7565, Structure et Réactivité des Systèmes Moléculaires Complexes - Equipe 5 (2MIC), Campus Bridoux - rue du Général Delestraint, 57070 Metz Cedex, France.
出版信息
Eur J Med Chem. 2015 Apr 13;94:102-12. doi: 10.1016/j.ejmech.2015.02.053. Epub 2015 Feb 28.
A series of 35 heteroarylimino-1,3-thiazolidinones with three sites of functionalization were synthesized and their antiproliferative properties were studied. The in vitro screening by MTT assay was performed against five cancer cell lines (human colon cancer cell lines HT29, HCT116 and SW620 and breast cancer cell lines MCF7 and MDA-MB-231). It was observed that N3-substituted thiazolidinones had moderate activities whereas 5-benzylidene thiazolidinones showed promising activities. To investigate the mechanism of action, detailed biological studies of six selected compounds (those presenting the lower mitotic index) were carried out on the human colon cancer HT29 cell line. Cell cycle assay revealed that those compounds induced cell accumulation in G2/M and in subG0/G1 phases of cell cycle. Moreover, dissipation of mitochondria membrane potential was observed as well as redox changes in treated cells.
合成了一系列具有三个官能化位点的35种杂芳基亚氨基-1,3-噻唑烷酮，并研究了它们的抗增殖特性。通过MTT法对五种癌细胞系（人结肠癌细胞系HT29、HCT116和SW620以及乳腺癌细胞系MCF7和MDA-MB-231）进行了体外筛选。观察到N3-取代的噻唑烷酮具有中等活性，而5-亚苄基噻唑烷酮显示出有前景的活性。为了研究作用机制，对人结肠癌细胞HT29细胞系进行了六种选定化合物（那些呈现较低有丝分裂指数的化合物）的详细生物学研究。细胞周期分析表明，这些化合物诱导细胞在细胞周期的G2/M期和subG0/G1期积累。此外，还观察到线粒体膜电位的消散以及处理细胞中的氧化还原变化。
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