2-Thiopyrimidine/chalcone hybrids: design, synthesis, ADMET prediction, and anticancer evaluation as STAT3/STAT5a inhibitors.

A novel 2-thiopyrimidine/chalcone hybrid was designed, synthesised, and evaluated for their cytotoxic activities against three different cell lines, K-562, MCF-7, and HT-29. The most active cytotoxic derivatives were , , , and (IC=0.77-1.74 µM, against K-562 cell line), and (IC=1.37-3.56 µM against MCF-7 cell line), and , , and (IC=2.10 and 2.37 µM against HT-29 cell line). Compounds , , , , and were further evaluated for their cytotoxicity against normal fibroblast cell line WI38. Moreover, STAT3 and STAT5a inhibitory activities were determined for the most active derivatives , , , , and . Dual inhibitory activity was observed in compound (IC=113.31 and 50.75 µM, against STAT3 and STAT5a, respectively). Prediction of physicochemical properties, drug likeness score, pharmacokinetic and toxic properties was detected.