Youssef Nehal A E, Selim Yasser A, Shaheen Lina A, Fadda Ahmed A, Gaffer Hatem E, El-Hadidy Sherihan A
Department of Chemistry, Faculty of Science, Mansoura University, Mansoura, 35516, Egypt.
Faculty of Specific Education, Zagazig University, Zagazig, 44519, Egypt.
Sci Rep. 2025 Jun 20;15(1):20155. doi: 10.1038/s41598-025-05325-1.
Many pyridopyrimidine moieties linked to the coumarin ring were synthesized by the reaction of malononitrile with 7-hydroxy-4-methyl-2-oxo-2 H-chromene-8-carbaldehyde (2) directly in the presence of ammonium acetate and different ketones and studied the effect of other basic catalysis, ratio of reactants and the effect of the solvent. The newly synthesized compounds were evaluated for their cytotoxic activity against four cell lines namely HepG2, WI-38, VERO, and MCF-7. The cytotoxic activity showed that compounds 8, 9, 10, and 7 have the highest activity against the studied cell lines. Focusing on the binding affinity and interactions between the five synthesized derivatives with the highest anticancer activity and specific amino acids of 4HJO residues over the molecular docking analysis. Derivative 10 recorded the highest energy score with good RMSD compared to the rest of the derivatives.
通过丙二腈与7-羟基-4-甲基-2-氧代-2H-色烯-8-甲醛(2)在乙酸铵和不同酮类存在下直接反应,合成了许多与香豆素环相连的吡啶并嘧啶部分,并研究了其他碱催化、反应物比例和溶剂的影响。对新合成的化合物针对四种细胞系(即HepG2、WI-38、VERO和MCF-7)的细胞毒性活性进行了评估。细胞毒性活性表明,化合物8、9、10和7对所研究的细胞系具有最高活性。通过分子对接分析,重点研究了五种具有最高抗癌活性的合成衍生物与4HJO残基的特定氨基酸之间的结合亲和力和相互作用。与其他衍生物相比,衍生物10记录的能量得分最高,且具有良好的均方根偏差(RMSD)。