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.
Copyright © 2014. Published by Elsevier Ltd.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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CD13 Antigens / antagonists & inhibitors
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CD13 Antigens / metabolism
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Dose-Response Relationship, Drug
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Drug Design*
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Drug Screening Assays, Antitumor
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HL-60 Cells
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Humans
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Matrix Metalloproteinase 2 / metabolism*
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Matrix Metalloproteinase Inhibitors / chemical synthesis
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Matrix Metalloproteinase Inhibitors / chemistry
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Matrix Metalloproteinase Inhibitors / pharmacology*
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Models, Molecular
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Molecular Structure
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Peptidomimetics / chemical synthesis
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Peptidomimetics / chemistry
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Peptidomimetics / pharmacology*
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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Matrix Metalloproteinase Inhibitors
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Peptidomimetics
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CD13 Antigens
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Matrix Metalloproteinase 2