Design, synthesis and preliminary evaluation of α-sulfonyl γ-(glycinyl-amino)proline peptidomimetics as matrix metalloproteinase inhibitors

Bioorg Med Chem. 2014 Jun 1;22(11):3055-64. doi: 10.1016/j.bmc.2013.12.025.

Jian Zhang ¹, Xiaoyang Li ², Yuqi Jiang ², Jinhong Feng ³, Xiaoguang Li ², Yingjie Zhang ², Wenfang Xu ⁴

Affiliations

1 Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44, West Wenhua Road, Ji'nan, Shandong 250012, China. Electronic address: zhangjian_3323@163.com.
2 Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44, West Wenhua Road, Ji'nan, Shandong 250012, China.
3 Shandong Analysis and Test Center, Shandong Academy of Sciences, Ji'nan, Shandong 250012, China.
4 Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44, West Wenhua Road, Ji'nan, Shandong 250012, China. Electronic address: wenfxu@gmail.com.

PMID: 24755524 DOI: 10.1016/j.bmc.2013.12.025

Abstract

A series of novel α-sulfonyl γ-(glycinyl-amino)proline peptidomimetic derivatives were designed, synthesized and assayed for their activities against matrix metalloproteinase-2 (MMP-2), Aminopeptidase N (APN)/CD13 and HDACs. The results indicated that all the compounds exhibited highly selective inhibition against MMP-2 as compared with APN and HDACs. The antiproliferative activities of some compounds against SKOV3, HL60 and A549 cells were also investigated. Comparing with the control LY52, compound 12u, with excellent activity both in the enzymatic inhibition assay and cell-based assay, could be used as lead compound for the further development of MMP inhibitors.

Keywords

Aminopeptidase N; HDACs; Hyp-Gly derivatives; Inhibitors; Matrix metalloproteinase-2; Synthesis.

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