Design, Synthesis and Biological Evaluation of Novel Non-peptide Boronic Acid Derivatives as Proteasome Inhibitors
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.
Keywords: Bortezomib, PI-083, proteasome inhibitors, drug design, non-peptide boronic acid derivatives.
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