摘要
A series of novel dipeptidyl boronic acid proteasome inhibitors constructed from aa-and aP-amino acids were designed and synthesized.Their structures were elucidated by ~1H NMR,~(13)C 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 aa-amino acids were as active as bortezomib.Interestingly,the activities of those derived from ap-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.
A series of novel dipeptidyl boronic acid proteasome inhibitors constructed from aa-and aP-amino acids were designed and synthesized.Their structures were elucidated by ~1H NMR,~(13)C 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 aa-amino acids were as active as bortezomib.Interestingly,the activities of those derived from ap-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.
引文
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