Design, synthesis and biological evaluation of novel pyrimidine-phenylsulfonylfuroxan hybrids
摘要
In this study, a series of novel pyrimidine-phenylsulfonylfuroxan hybrids were designed, synthesized and evaluated for their biological activities. Most of the compounds demonstrated considerable antiproliferative activity against MDA-MB-231 and PC-3 cells. Among them, 21y (IC50 = 0.82 ± 0.08 μM) possessed excellent antiproliferative activity against PC-3 in vitro, significantly superior to the positive control drug 5-FU, which inhibited PC-3 colony formation and migration ability in a dose-dependent manner and blocked the cell cycle at the GO/G1 phase. Furthermore, 21y dramatically induced apoptosis of PC-3 cells via the mitochondrial pathway, the ROS pathway, and the regulation of apoptosis-related proteins. Notably, the high-level NO generated by 21y in PC-3 cells had a synergistic antitumor effect. With these results, compound 21y could act as an antitumor candidate with potential for further studies.