Design, synthesis, biological evaluation and molecular docking of novel isatin-oxime ether derivatives as potential IDH1 inhibitors.

A series of novel isatin-oxime ether derivatives were designed, synthesized and characterized by ¹ H NMR and ¹³ C NMR and HRMS. These compounds were evaluated for their in vitro cytotoxicity against three human cancer cell lines (A549, HepG2 and Hela) by MTT assay. According to the experimental results, compounds 6a (IC ₅₀  = 0.34μM), 6c (IC ₅₀  = 14nM) and 6r (IC ₅₀  = 45nM) were found as the excellent selectivity and high activity against A549, whereas compounds 6m (IC ₅₀  = 12nM) and 6n (IC ₅₀  = 25nM) displayed the significant activity for HepG2, respectively. Compound 6f (IC ₅₀  = 30nM), 6n (IC ₅₀  = 9nM) and 6o (IC ₅₀  = 20nM) also showed the excellent activity against Hela. From the experiments of cell migration and colony formation assays, the findings demonstrated that 6m can effectively suppress the migration and growth of HepG2 cells. In addition, the results of molecular docking studies determined the strong binding interactions between the potential active compounds 6m and 6n and the active sites of isocitrate dehydrogenase 1 (IDH1) with the lowest binding affinity energy.
Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests.
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