Abstract

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 9d, 9f, 9n, and 9p (IC₅₀=0.77–1.74 µM, against K-562 cell line), 9a and 9r (IC₅₀=1.37–3.56 µM against MCF-7 cell line), and 9a, 9l, and 9n (IC₅₀=2.10 and 2.37 µM against HT-29 cell line). Compounds 9a, 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 µM, against STAT3 and STAT5a, respectively). Prediction of physicochemical properties, drug likeness score, pharmacokinetic and toxic properties was detected.

 抽象的

设计、合成了一种新型 2-硫代嘧啶/查耳酮杂化物，并评估了其针对三种不同细胞系 K-562、MCF-7 和 HT-29 的细胞毒活性。最活跃的细胞毒性衍生物是9d 、 9f 、 9n和9p （针对 K-562 细胞系，IC ₅₀ =0.77–1.74 µM）、 9a和9r （针对 MCF-7 细胞系，IC ₅₀ =1.37–3.56 µM），和9a 、 9l和9n （针对HT-29细胞系的IC ₅₀ =2.10和2.37μM）。进一步评估化合物9a 、 9d 、 9f 、 9n和9r针对正常成纤维细胞系WI38的细胞毒性。此外，还确定了最活跃的衍生物9a 、 9d 、 9f 、 9n和9r 的STAT3 和 STAT5a 抑制活性。在化合物9n中观察到双重抑制活性（针对 STAT3 和 STAT5a 的 IC ₅₀分别为 113.31 和 50.75 µM）。检测理化性质、药物相似度评分、药代动力学和毒性性质的预测。