2-(4-氯苄基)-6-芳基咪唑并[2,1-b][1,3,4]噻二唑：合成、细胞毒性活性及作用机制。
2-(4-Chlorobenzyl)-6-arylimidazo[2,1-b][1,3,4]thiadiazoles: synthesis, cytotoxic activity and mechanism of action.
机构信息
Department of Pharmaceutical Chemistry, KLE University's College of Pharmacy, Bangalore 560010, India.
Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India.
出版信息
Eur J Med Chem. 2014 Sep 12;84:687-97. doi: 10.1016/j.ejmech.2014.07.054. Epub 2014 Jul 17.
The cytotoxic activity of a new series of 2-(4'-chlorobenzyl)-5,6-disubstituted imidazo[2,1-b][1,3,4]thiadiazoles against different human and murine cancer cell lines is reported. Among the tested compounds, two derivatives namely 2-(4-chlorobenzyl)-6-(2-oxo-2H-chromen-3-yl)imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde 4i and 2-(4-chlorobenzyl)-6-(2-oxo-2H-chromen-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl thiocyanate 5i emerged as the most potent against all the cell lines. To investigate the mechanism of action, we selected compounds 4i for cell cycle study, analysis of mitochondrial membrane potential and Annexin V-FITC flow cytometric analysis and DNA fragmentation assay. Results showed that 4i induced cytotoxicity by inducing apoptosis without arresting the cell cycle.
报告了一系列新型 2-(4'-氯苄基)-5,6-取代咪唑并[2,1-b][1,3,4]噻二唑对不同人源和鼠源癌细胞系的细胞毒性活性。在所测试的化合物中，两种衍生物，即 2-(4-氯苄基)-6-(2-氧代-2H-色烯-3-基)咪唑并[2,1-b][1,3,4]噻二唑-5-甲酰基醛 4i 和 2-(4-氯苄基)-6-(2-氧代-2H-色烯-3-基)咪唑并[2,1-b][1,3,4]噻二唑-5-巯基氰基 5i，对所有细胞系均表现出最强的活性。为了研究作用机制，我们选择化合物 4i 进行细胞周期研究、线粒体膜电位分析、Annexin V-FITC 流式细胞术分析和 DNA 片段化分析。结果表明，4i 通过诱导细胞凋亡而不是阻断细胞周期来诱导细胞毒性。
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