Design, synthesis and biological activity of non-nucleoside NEDD8-activating enzyme inhibitors
10.3969/j.issn.1006-0111.201901012
- VernacularTitle:非核苷类NEDD8活化酶抑制剂的设计、合成与活性研究
- Author:
Chuan LUO
1
;
Zhiliang YU
2
;
Wannian ZHANG
2
;
Zhenyuan MIAO
3
Author Information
1. Anhui Huarun Golden Frog Pharmaceutical Co., Ltd., Huaibei 235000, China.
2. Department of Medicinal Chemistry, School of Pharmacy, Naval Medical University, Shanghai 200433, China.
3. Department of Medicinal Chemistry, School of Pharmacy, Naval Medical University, Shanghai 200433, China.miaozhenyuan@hotmail.com
- Keywords:
NAE;
indazole;
scaffold hopping;
antitumor activity;
in vitro
- From:
Journal of Pharmaceutical Practice
2020;38(1):35-41
- CountryChina
- Language:Chinese
-
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.
