Novel 2,4-thiazolidinediones: Synthesis, in vitro cytotoxic activity, and mechanistic investigation

作者：Metwally Kamel^*; Pratsinis Harris; Kletsas Dimitris

来源：European Journal of Medicinal Chemistry, 2017, 133: 340-350.

DOI：10.1016/j.ejmech.2017.03.052

• The glitazones
• Thiazolidinediones
• Anticancer
• Apoptosis

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.

• 出版日期2017-6-16