Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.
J Enzyme Inhib Med Chem. 2020 Dec;35(1):864-879. doi: 10.1080/14756366.2020.1740922.
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.
设计、合成了一种新型的 2-嘧啶/查尔酮杂合体，并对其在三种不同细胞系（K-562、MCF-7 和 HT-29）中的细胞毒性进行了评价。最具活性的细胞毒性衍生物为 、 、 和 （IC=0.77-1.74µM，针对 K-562 细胞系）、 和 （IC=1.37-3.56µM，针对 MCF-7 细胞系）以及 、 、 和 （IC=2.10 和 2.37µM，针对 HT-29 细胞系）。进一步对化合物 、 、 、 和 进行了针对正常成纤维细胞系 WI38 的细胞毒性评价。此外，还对最具活性的衍生物 、 、 、 和 进行了 STAT3 和 STAT5a 抑制活性的测定。在化合物 （IC=113.31 和 50.75µM，针对 STAT3 和 STAT5a，分别）中观察到双重抑制活性。还检测了预测的物理化学性质、药物相似性评分、药代动力学和毒性特性。
