Leicester School of Pharmacy, De Montfort University, Leicester LE1 9BH, UK.
Faculty of Pharmacy, University Business Academy, 21000 Novi Sad, Serbia.
Molecules. 2024 Sep 24;29(19):4539. doi: 10.3390/molecules29194539.
A focussed library of pyridyl and 2-hydroxyphenyl chalcones were synthesized and tested for growth inhibitory activity against H37Rv, and normal and cancer breast cell lines. Pyridyl chalcones bearing lipophilic A-ring, e.g., dichloro-phenyl-(), pyrene-1-yl ()- and biphenyl-4-yl () moieties were found to be the most potent of the series inhibiting the growth of H37Rv with IC values ranging from 8.9-28 µM. Aryl chalcones containing a 3-methoxyphenyl A-ring and either -Br-phenyl () or -Cl-phenyl () B-rings showed an IC value of 28 µM. Aryl-chalcones were generally less toxic to HepG2 cells compared to pyridyl-chalcones. Dose-dependent antiproliferative activity against MDA468 cells was observed for trimethoxy-phenyl () and anthracene-9-yl () pyridyl-chalcones with IC values of 0.7 and 0.3 µM, respectively. Docking studies revealed that chalone was predicted to bind to the protein tyrosine phosphatases B (PtpB) with higher affinity compared to a previously reported PtpB inhibitor.
我们合成了一个聚焦的吡啶基和 2-羟基苯基查耳酮库，并测试了它们对 H37Rv 以及正常和乳腺癌细胞系的生长抑制活性。带有亲脂性 A 环的吡啶查耳酮，例如二氯苯基()、芘-1-基()和联苯-4-基()部分，是该系列中最有效的，抑制 H37Rv 生长的 IC 值范围为 8.9-28µM。含有 3-甲氧基苯基 A 环的芳基查耳酮，无论是 -Br-苯基()还是 -Cl-苯基()B 环，IC 值均为 28µM。与吡啶查耳酮相比，芳基查耳酮通常对 HepG2 细胞的毒性较小。三甲氧基苯基()和蒽-9-基()吡啶查耳酮对 MDA468 细胞的增殖活性呈剂量依赖性，IC 值分别为 0.7 和 0.3µM。对接研究表明，与先前报道的 PtpB 抑制剂相比，查耳酮与蛋白酪氨酸磷酸酶 B (PtpB) 的结合亲和力更高。
