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

摘要

A novel 2-thiopyrimidine/chalcone hybrid was designed, synthesised, and evaluated for their cytotoxicactivities against three different cell lines, K-562, MCF-7, and HT-29. The most active cytotoxic derivativeswere 9d, 9f, 9n, and 9p (IC50?0.77–1.74 mM, against K-562 cell line), 9a and 9r (IC50?1.37–3.56 mMagainst MCF-7 cell line), and 9a, 9l, and 9n (IC50?2.10 and 2.37 mM against HT-29 cell line). Compounds9a, 9d, 9f, 9n, and 9r 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 9a, 9d,9f, 9n, and 9r. Dual inhibitory activity was observed in compound 9n (IC50?113.31 and 50.75 mM, againstSTAT3 and STAT5a, respectively). Prediction of physicochemical properties, drug likeness score, pharmacokineticand toxic properties was detected.