Hybrids of 1,2,3,4‐Tetrahydroisoquinoline‐Isatin as Potential CDK ‐5 Inhibitors: Synthesis, Biological Evaluations, and Molecular Docking Studies

ABSTRACT In this study, we have designed and synthesized a series of novel 1,2,3,4‐tetrahydroisoquinoline‐isatin derivatives, which were characterized by 1 H NMR and 13 C NMR and HRMS. These compounds were evaluated for their potential anticancer activities against three human cancer cell lines (A549, HepG2 and Hela) by MTT assay in vitro. According to the IC 50 values, most of the compounds showed high activities against A549 (IC 50 = 6.47–25.08 μM), HepG2 (IC 50 = 2.55–46.85 μM), and Hela (IC 50 = 0.0067–87.35 μM), respectively. In particular, compound 6g showed the highest activity and selectivity against Hela (IC 50 = 6.7 nM). The results of cell migration and colony formation assays suggested that compounds ( 6k , 6m , and 6n ) can effectively suppress the migration and growth of A549, HepG2, and Hela cells. In addition, the strong interaction and excellent binding affinity between potential active compounds ( 6g , 6p and 6q ) and the active sites of CDK‐5 were confirmed by molecular docking studies. Therefore, 1,2,3,4‐tetrahydroisoquinoline‐isatin hybrids might be considered as promising lead scaffolds for CDK‐5 inhibitors.