Document Detail


Stictamides A-C, MMP12 inhibitors containing 4-amino-3-hydroxy-5-phenylpentanoic acid subunits.
MedLine Citation:
PMID:  21500817     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
An extensive study of the secondary metabolites produced by a new Sticta sp. of lichen has led to the isolation of three new compounds containing the 4-amino-3-hydroxy-5-phenylpentanoic acid residue (Ahppa). The structures of stictamides A-C (1-3) were assigned by 2D NMR spectroscopic and chemical methods. Due to extensive epimerization of the Ahppa residue observed after acid hydrolysis, the configuration of this unit was deduced through conversion of 1 to an appropriate derivative and application of our recently developed statine NMR database. Evaluation of stictamide A against a panel of disease-relevant proteases showed that it inhibited MMP12 at 2.3 μM and significantly reduced invasion in the human glioma cell line U87MG. Docking studies suggest that stictamide A inhibits MMP12 by a non-zinc-binding mechanism.
Authors:
Zhibin Liang; Analia Sorribas; Florian J Sulzmaier; Jorge I Jiménez; Xin Wang; Thomas Sauvage; Wesley Y Yoshida; Guangyi Wang; Joe W Ramos; Philip G Williams
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2011-04-18
Journal Detail:
Title:  The Journal of organic chemistry     Volume:  76     ISSN:  1520-6904     ISO Abbreviation:  J. Org. Chem.     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-05-13     Completed Date:  2011-09-09     Revised Date:  2012-04-12    
Medline Journal Info:
Nlm Unique ID:  2985193R     Medline TA:  J Org Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3635-43     Citation Subset:  IM    
Affiliation:
Departmentsof Chemistry, University of Hawaii at Manoa, Honolulu, Hawaii 96822, United States.
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MeSH Terms
Descriptor/Qualifier:
Amino Acids / chemistry*
Cell Line, Tumor
Cell Survival / drug effects
Humans
Matrix Metalloproteinase 12 / antagonists & inhibitors*,  chemistry
Models, Molecular
Neoplasm Invasiveness
Peptides / chemistry*,  pharmacology*
Protease Inhibitors / chemistry*,  pharmacology*
Protein Conformation
Grant Support
ID/Acronym/Agency:
1R21AG032405/AG/NIA NIH HHS; R01 GM088266-01A1/GM/NIGMS NIH HHS; R01 GM088266-02/GM/NIGMS NIH HHS; R01GM088266/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Amino Acids; 0/Peptides; 0/Protease Inhibitors; 72155-51-2/4-amino-3-hydroxy-5-phenylpentanoic acid; EC 3.4.24.65/Matrix Metalloproteinase 12

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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