Abstract
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.
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•Two thiazolidinedione scaffolds different in the position of the thiazolidinedione ring in the molecule were synthesized.•The target compounds were tested for in vitro cytotoxic activity in three human cancer cell lines.•Some of the target compounds displayed cytotoxic activity in the low micromolar range.•Mechanistic investigation revealed pro-apoptotic activity of the most cytotoxic compounds.•Key signaling mechanisms were investigated and found to vary depending on the target cell context.