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Abstract <p><b>Objective:</b> Based on the observed in vitro antitumor activity, the conformational influence of various substituents at the 2-position of the pyrimidine ring was systematically investigated to develop more effective antitumor pyrimidine analogs. <b>Methods:</b> A series of novel pyrimidine derivatives containing acrylamide and cyano groups were designed and synthesized. Their antiproliferative activities against four human tumor cell lines (MDA-MB-231, MGC-803, PC-3, and A549) were evaluated using the MTT assay. Additionally, colony formation, migration, cell cycle distribution, and apoptosis assays were performed to elucidate the antitumor mechanisms of compound (<b>XVIIIg</b>). <b>Results and Discussion:</b> Compound (<b>XVIIIg</b>) exhibited the strongest inhibitory activity against PC-3 cells, with an IC<sub>50</sub> value of 1.50 ± 0.29 μM. Cellular assays confirmed that (<b>XVIIIg</b>) significantly suppressed PC-3 cell proliferation and migration, induced G<sub>0</sub>/G<sub>1</sub> cell cycle arrest, and promoted apoptosis. Structural modifications at the 2-position of the pyrimidine ring had a pronounced effect on <i>in vitro</i> antitumor activity. The 4-fluorophenyl (4-F-C<sub>6</sub>H<sub>4</sub>) substituent in compound (<b>XVIIIg</b>) contributed to its superior inhibitory effect, suggesting its potential as a lead compound. <b>Conclusions:</b> Among the 21 synthesized compounds, (<b>XVIIIg</b>) demonstrated the most potent antiproliferative and antimigratory activity, along with dose-dependent apoptosis induction in PC-3 cells. These results highlight its promise as a candidate for further development of novel antitumor agents.</p>

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Design, Synthesis, and Evaluation of Antitumor Activity of Novel Pyrimidine Derivatives Containing Acrylamide and a Cyano Group

  • 期刊论文

  • 发表日期：

    2025年6月3日

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  • Hongjing Chen,
  • Dongling Gu,
  • Jiahui Han,
  • Zichen Yang,
  • Shihao Wang,
  • Lingling Chi,
  • Fuqiang Yu,
  • Hao Wang,
  • Hongmin Liu,
  • Yu Ke,
  • Qiurong Zhang

摘要

Abstract

Objective: Based on the observed in vitro antitumor activity, the conformational influence of various substituents at the 2-position of the pyrimidine ring was systematically investigated to develop more effective antitumor pyrimidine analogs. Methods: A series of novel pyrimidine derivatives containing acrylamide and cyano groups were designed and synthesized. Their antiproliferative activities against four human tumor cell lines (MDA-MB-231, MGC-803, PC-3, and A549) were evaluated using the MTT assay. Additionally, colony formation, migration, cell cycle distribution, and apoptosis assays were performed to elucidate the antitumor mechanisms of compound (XVIIIg). Results and Discussion: Compound (XVIIIg) exhibited the strongest inhibitory activity against PC-3 cells, with an IC50 value of 1.50 ± 0.29 μM. Cellular assays confirmed that (XVIIIg) significantly suppressed PC-3 cell proliferation and migration, induced G0/G1 cell cycle arrest, and promoted apoptosis. Structural modifications at the 2-position of the pyrimidine ring had a pronounced effect on in vitro antitumor activity. The 4-fluorophenyl (4-F-C6H4) substituent in compound (XVIIIg) contributed to its superior inhibitory effect, suggesting its potential as a lead compound. Conclusions: Among the 21 synthesized compounds, (XVIIIg) demonstrated the most potent antiproliferative and antimigratory activity, along with dose-dependent apoptosis induction in PC-3 cells. These results highlight its promise as a candidate for further development of novel antitumor agents.