Metwally Kamel, Pratsinis Harris, Kletsas Dimitris
Department of Medicinal Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
Laboratory of Cell Proliferation and Ageing, Institute of Biosciences and Applications, National Centre of Scientific Research "Demokritos", Athens, Greece.
Eur J Med Chem. 2017 Jun 16;133:340-350. doi: 10.1016/j.ejmech.2017.03.052. Epub 2017 Mar 25.
Two thiazolidinedione scaffolds different in the position of the thiazolidinedione ring in the molecule were tested for in vitro cytotoxic activity in a panel of human cancer cell lines namely, prostate cancer cells PC-3, breast carcinoma cells MDA-MB-231, and fibrosarcoma cells HT-1080. Some of the target compounds of the A-series where the thiazolidinedione ring is terminal, displayed cytotoxic activity in the low micromolar range in the cell lines tested. Target thiazolidinediones of the B-series where the thiazolidinedione ring is located in the middle of the molecule showed cytotoxic activity comparable to that of their A-series counterparts. Our mechanistic studies indicated that the most cytotoxic compounds in this study have pro-apoptotic capacity. Key signaling mechanisms were investigated and found to vary depending on the target cell context, in line with previous observations regarding thiazolidinediones.
对分子中噻唑烷二酮环位置不同的两种噻唑烷二酮骨架进行了体外细胞毒性活性测试，测试对象为一组人类癌细胞系，即前列腺癌细胞PC-3、乳腺癌细胞MDA-MB-231和纤维肉瘤细胞HT-1080。噻唑烷二酮环位于末端的A系列中的一些目标化合物，在测试的细胞系中显示出低微摩尔范围内的细胞毒性活性。噻唑烷二酮环位于分子中间的B系列目标噻唑烷二酮显示出与A系列对应物相当的细胞毒性活性。我们的机制研究表明，本研究中细胞毒性最强的化合物具有促凋亡能力。研究了关键信号机制，发现其因靶细胞环境而异，这与先前关于噻唑烷二酮的观察结果一致。
