Design, synthesis and antitumor activity of isatin derivatives as palmitoyl transferase inhibitors

Based on the chemical structure of known compound, 12 isatin derivatives palmitoyl transferase inhibitors are designed and synthesized using bioisosterism and molecular docking, while their anti-tumor activities in vitro are determined. The structures of the target compounds are confirmed by ¹H NMR, ¹³C NMR and HR-MS. In vitro anti-tumor assay illustrates that compound 5b exhibits similar anti-tumor activity to the control (IC₅₀=8.4 μmol·L^-1), with IC₅₀ value of 12.0 μmol·L^-1 against MCF-7 in which palmitoyl transferase is highly expressed. Compound 4b shows higher inhibitory activity against HeLa (IC₅₀=8.1 μmol·L^-1) than cisplatin (IC₅₀=40.1 μmol·L^-1). The molecular docking demonstrates that all compounds could completely enter the site of 3'-adenosine monophosphate-5'-diphosphate (PAP). Taken together, isatin derivatives represent promising compounds for the discovery of novel anti-tumor agents.