【摘 要】
：
A series of novel dipeptidyl boronic acid proteasome inhibitors constructed from αα-and αβ-amino acids were designed and synthesized.Their structures were elucidated by 1H NMR,13C NMR, LC-MS and HRMS.
【机 构】
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Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21
【出 处】
：
中国药学会第十三届青年药学科研成果交流会
论文部分内容阅读
A series of novel dipeptidyl boronic acid proteasome inhibitors constructed from αα-and αβ-amino acids were designed and synthesized.Their structures were elucidated by 1H NMR,13C NMR, LC-MS and HRMS.These compounds were evaluated for their b5 subunit inhibitory activities of human proteasome.The results showed that dipeptidyl boronic acid inhibitors composed of αα-amino acids were as active as bortezomib.Interestingly, the activities of those derived from αβ-amino acids lost completely.Of all the inhibitors, compound 22 (IC50 =4.82 nM) was the most potent for the inhibition of proteasome activity.Compound 22 was also the most active against three MM cell lines with IC50 values less than 5 nM in inhibiting cell growth assays.Molecular docking studies displayed that 22 fitted very well in the b5 subunit active pocket of proteasome.
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