Design, synthesis and biological activity of non-nucleoside NEDD8-activating enzyme inhibitors / 药学实践杂志
Journal of Pharmaceutical Practice
; (6): 35-41, 2020.
Article
en Zh
| WPRIM
| ID: wpr-782381
Biblioteca responsable:
WPRO
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.
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Base de datos:
WPRIM
Idioma:
Zh
Revista:
Journal of Pharmaceutical Practice
Año:
2020
Tipo del documento:
Article