Design, synthesis and biological activity of non-nucleoside NEDD8-activating enzyme inhibitors / 药学实践杂志

ABSTRACT

Objective To develop novel NAE inhibitors with non-nucleoside scaffold by a scaffold hopping strategy and study the in vitro antitumor activities. Methods Disulfonamideindazole 14 was synthesized through 23 steps with a good yield. Its chemical structure was confirmed by 1H NMR and MS. MTT method was used to determine the in vitro antitumor activities. Results Compound 14 exhibited moderate antitumor activities against various cancer cells and promoted significant UBC12 accumulation in a dose-dependent manner. Conclusion Compound 14 is a potent NAE inhibitor with remarkable apoptosis induction and cell cycle arrest in prostate cancer PANC-1 cells. Our work provides a valuable leading compound for the further design and development of NAE inhibitors.