Department of Food, Environmental and Nutritional Sciences (DeFENS), Università degli Studi di Milano, Via Celoria 2, 20133 Milan, Italy.
Department of Pharmacy, Division of Pharmaceutical Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, 15771 Athens, Greece.
Int J Mol Sci. 2023 Sep 20;24(18):14346. doi: 10.3390/ijms241814346.
Novel amino-substituted pyridoquinazolinone derivatives have been designed and synthesized as potential c-MYC G-quadruplex (G4) ligands, employing an efficient methodology. All the new compounds exhibited moderate to good antiproliferative activity against the human osteosarcoma U2OS cell line. NMR and docking experiments revealed that the recently synthesized compounds interact with the Pu22 G-quadruplex in the c-MYC promoter region, establishing a 2:1 complex, with each molecule positioned over the tetrads at the 3'- and 5'-ends.
新型氨基取代的吡啶并喹唑啉酮衍生物已被设计和合成，作为潜在的 c-MYC G-四链体 (G4) 配体，采用了一种高效的方法。所有新化合物对人骨肉瘤 U2OS 细胞系均表现出中等至良好的抗增殖活性。NMR 和对接实验表明，最近合成的化合物与 c-MYC 启动子区域的 Pu22 G-四链体相互作用，形成 2:1 的复合物，每个分子位于四联体的 3'-和 5'-末端。
