Noser Ahmed A, Salem Maha M, ElSafty Esraa M, Baren Mohamed H, Selim Adel I, Mandour Hamada S A
Organic Chemistry, Chemistry Department, Faculty of Science, Tanta University Tanta 31527 Egypt
Biochemistry Division, Chemistry Department, Faculty of Science, Tanta University Tanta 31527 Egypt
RSC Adv. 2025 Apr 25;15(17):13214-13224. doi: 10.1039/d5ra01233c. eCollection 2025 Apr 22.
Heterocyclic compounds are essential to the drug development and discovery processes. Herein, we synthesized new pyrazolone chalcones (3a-g) through the reaction of azopyrazolone (2) with different aromatic aldehydes in a basic medium. Numerous techniques including elemental analysis, H-NMR, C-NMR, and FT-IR spectroscopies, were used to characterize pyrazolone chalcone derivatives. Compound 3b exhibited the highest binding energy towards YAP/TEAD protein with a value of -8.45 kcal mol in studies. This observation suggested that compound 3b inhibits the YAP/TEAD Hippo signaling pathway. In addition, compound 3b offered a prospective anticancer effect against various cancer cell lines, such as HepG-2, MCF-7, and HCT-116, among the other synthesized compounds, with IC values equal to 5.03 ± 0.4, 3.92 ± 0.2, and 6.34 ± 0.5 μM, respectively. These results validated our findings regarding the suppression of the YAP/TEAD protein. Its pharmacokinetic properties were theoretically observed using ADMET. Additionally, compound 3b demonstrated a potent antioxidant scavenging action () against DPPH free radicals. Thus, based on our findings, compound 3b may act as a potential anticancer scaffold owing to its inhibitory impact towards the YAP/TEAD-mediated Hippo signaling pathway with a safe toxic profile on normal cells.
杂环化合物对药物开发和发现过程至关重要。在此，我们通过偶氮吡唑啉酮（2）与不同芳香醛在碱性介质中的反应合成了新型吡唑啉酮查耳酮（3a - g）。使用了包括元素分析、H - NMR、C - NMR和FT - IR光谱等多种技术来表征吡唑啉酮查耳酮衍生物。在研究中，化合物3b对YAP/TEAD蛋白表现出最高的结合能，值为 - 8.45 kcal/mol。这一观察结果表明化合物3b抑制YAP/TEAD Hippo信号通路。此外，在其他合成化合物中，化合物3b对多种癌细胞系，如HepG - 2、MCF - 7和HCT - 116，具有预期的抗癌作用，IC值分别等于5.03±0.4、3.92±0.2和6.34±0.5 μM。这些结果验证了我们关于YAP/TEAD蛋白抑制作用的发现。使用ADMET理论上观察了其药代动力学性质。此外，化合物3b对DPPH自由基表现出有效的抗氧化清除作用（）。因此，基于我们的发现，化合物3b可能因其对YAP/TEAD介导的Hippo信号通路的抑制作用以及对正常细胞安全的毒性特征而作为一种潜在的抗癌支架。
