title: Design, synthesis and biological evaluation of novel non-peptide boronic acid derivatives as proteasome inhibitors.
abstract: A series of novel non-peptide boronic acid derivatives were designed and synthesized via rational drug design principles. All target compounds were screened for the proteasome inhibitory activities in vitro. Selected compounds (6a and 7j) were evaluated for their cytotoxic activities in vitro. Among these tested compounds, two (6a, 7j) displayed better proteasome inhibitory activities than that of the lead compound PI-083, and compound 6a was the most potent one with IC₅₀ value of 161.90±29.46 nM. However, both of the two compounds (6a, 7j) exhibited weak cytotoxic activities, the discrepancy may lie in the compensatory pathways of the ubiquitin-proteasome pathway that promote tumor cell survival.
authors.forename: Jiankang
authors.initials: J
authors.lastname: Zhang
authors.forename: Luqing
authors.initials: L
authors.lastname: Shen
authors.forename: Jincheng
authors.initials: J
authors.lastname: Wang
authors.forename: Peihua
authors.initials: P
authors.lastname: Luo
authors.affiliation: ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. huyz@zju.edu.cn.
authors.forename: Yongzhou
authors.initials: Y
authors.lastname: Hu
mesh_terms: D001897:Boronic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry; D061988:Proteasome Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D001897:Boronic Acids; D010455:Peptides; D061988:Proteasome Inhibitors