Design,synthesis and docking studies of novel dipeptidyl boronic acid proteasome inhibitors constructed from αα-and αβ-amino acids
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- 英文论文题名：Design,synthesis and docking studies of novel dipeptidyl boronic acid proteasome inhibitors constructed from αα-and αβ-amino acids
- 论文作者：Jingmiao Shi ; Meng Lei ; Wenkui Wu ; Huayun Feng ; Jia Wang ; Shanshan Chen ; Yongqiang Zhu ; Shihe Hu ; Zhaogang Liu ; Cheng Jiang
- 英文论文作者：Jingmiao Shi ; Meng Lei ; Wenkui Wu ; Huayun Feng ; Jia Wang ; Shanshan Chen ; Yongqiang Zhu ; Shihe Hu ; Zhaogang Liu ; Cheng Jiang ; Jiang Su Key Laboratory of Drug Design and Optimization ; China Pharmaceutical University ; Department of Medicinal Chemistry ; School of Pharmacy ; China Pharmaceutical University ; College of Science ; Nanjing Forestry University ; College of Life Science ; Nanjing Normal University ; Jiangsu Chia Tai Fenghai Pharmaceutical Co.Ltd
- 年：2016
- 作者机构：Jiang Su Key Laboratory of Drug Design and Optimization,China Pharmaceutical University;Department of Medicinal Chemistry,School of Pharmacy,China Pharmaceutical University;College of Science,Nanjing Forestry University;College of Life Science,Nanjing Normal University;Jiangsu Chia Tai Fenghai Pharmaceutical Co.Ltd;
- 英文论文关键词：Proteasome inhibitor ; Dipeptidyl boronic acid ; Structure-activity relationship ; Cytotoxicity ; Docking study
- 会议召开时间：2016-09-27
- 会议录名称：中国药学会第十三届青年药学科研成果交流会论文集
- 语种：英文
- 分类号：R91;R914.5
- 学会代码：YYWS
- 会议名称：中国药学会第十三届青年药学科研成果交流会
- 会议地点：中国江西南昌
- 主办单位：中国药学会
- 学会名称：中国药学会
- 页数：1
- 文件大小：44k
- 原文格式：O
- 会议级别：全国
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.
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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