Lee Yu-Ru, Chen Tsung-Chih, Lee Chia-Chung, Chen Chun-Liang, Ahmed Ali Ahmed Atef, Tikhomirov Alexander, Guh Jih-Hwa, Yu Dah-Shyong, Huang Hsu-Shan
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan; Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan.
Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan.
Eur J Med Chem. 2015 Sep 18;102:661-76. doi: 10.1016/j.ejmech.2015.07.052. Epub 2015 Aug 7.
A series of sulfur-substituted anthra[1,2-c][1,2,5]thiadiazole-6,11-diones were synthesized and evaluated using the cell proliferations, apoptosis and NCI-60 cell panel assays. Also, the signaling pathways that account for their activities were investigated. Compounds 2, 3, 4a, 4d, 4f, 4i, 4k, 5b, 5c, 5d, 5f, 5g, 6b, 6c, 6d, 6e, 6g, 7a and 7g were selected by NCI. Among the tested compounds, 6g appeared to be the most active compound of this series that not only induced apoptosis in DU-145 cancer cells but also attenuated the ERK1/2 and p38 signaling pathways. All test compounds exhibited diverse cytostatic and cytotoxic activities that warrant further development as potential anticancer agents.
合成了一系列硫取代的蒽[1,2 - c][1,2,5]噻二唑 - 6,11 - 二酮，并通过细胞增殖、凋亡和NCI - 60细胞系检测进行评估。此外，还研究了导致其活性的信号通路。化合物2、3、4a、4d、4f、4i、4k、5b、5c、5d、5f、5g、6b、6c、6d、6e、6g、7a和7g被NCI选中。在所测试的化合物中，6g似乎是该系列中最具活性的化合物，它不仅能诱导DU - 145癌细胞凋亡，还能减弱ERK1/2和p38信号通路。所有测试化合物均表现出不同的细胞生长抑制和细胞毒性活性，值得作为潜在的抗癌药物进一步开发。
