2. Academic Validation
  3. Design, synthesis, and biological evaluation of novel phenol ether derivatives as non-covalent proteasome inhibitors

Design, synthesis, and biological evaluation of novel phenol ether derivatives as non-covalent proteasome inhibitors

  • Eur J Med Chem. 2019 Jan 1:161:543-558. doi: 10.1016/j.ejmech.2018.10.056.
Jianjun Yu 1,  Lei Xu 2,  Duidui Hong 1,  Xiaotuan Zhang 3,  Jieyu Liu 3,  Daqiang Li 1,  Jia Li 3,  Yubo Zhou 4,  Tao Liu 5
Affiliations

Affiliations

  • 1 ZJU-ENS Joint Laboratory of Medicinal Chemistry, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China.
  • 2 School of Life Science and Technology, ShanghaiTech University, Shanghai, 201203, PR China; National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, PR China; University of Chinese Academy of Sciences, Graduate School, No. 19A Yuquan Road, Beijing, 100049, PR China.
  • 3 National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, PR China; University of Chinese Academy of Sciences, Graduate School, No. 19A Yuquan Road, Beijing, 100049, PR China.
  • 4 National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, PR China; University of Chinese Academy of Sciences, Graduate School, No. 19A Yuquan Road, Beijing, 100049, PR China. Electronic address: ybzhou@simm.ac.cn.
  • 5 ZJU-ENS Joint Laboratory of Medicinal Chemistry, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China. Electronic address: Lt601@zju.edu.cn.
PMID: 30391816 DOI: 10.1016/j.ejmech.2018.10.056
Abstract

A series of novel phenol ether derivatives were designed, synthesized, and evaluated as non-covalent Proteasome inhibitors. Most compounds exhibited moderate to excellent Proteasome inhibitory activity. In particular, compound 18x proved to be the most potent compound (chymotrypsin-like: IC50 = 49 nM), exhibiting a 2-fold higher potency compared to the reported PI-1840. Besides, compound 18x exhibited excellent metabolic stability and selective anti-proliferative activity against solid Cancer cell lines including HepG2 and HGC27, providing incentive for the further development as a potential Anticancer agent against solid cancers.

Keywords

Non-covalent; Non-peptide; Phenol ether; Proteasome inhibitor; Solid cancers.

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