Selective inhibition of matrix metalloproteinase isozymes and in vivo protection against emphysema by substituted gamma-keto carboxylic acids

Dawei Ma; Yongwen Jiang; Fangping Chen; Li-kun Gong; Ke Ding; Yong Xu; Renxiao Wang; Aihua Ge; Jin Ren; Jingya Li; Jia Li; Qizhuang Ye

doi:10.1021/jm051101g

Selective inhibition of matrix metalloproteinase isozymes and in vivo protection against emphysema by substituted gamma-keto carboxylic acids

J Med Chem. 2006 Jan 26;49(2):456-8. doi: 10.1021/jm051101g.

Authors

Dawei Ma¹, Yongwen Jiang, Fangping Chen, Li-kun Gong, Ke Ding, Yong Xu, Renxiao Wang, Aihua Ge, Jin Ren, Jingya Li, Jia Li, Qizhuang Ye

Affiliation

¹ State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China. madw@mail.sioc.ac.cn

PMID: 16420030
DOI: 10.1021/jm051101g

Abstract

The synthesis and matrix metalloproteinase (MMP) inhibitory activity of a series of gamma-keto carboxylic acids are described. Among nine MMP isozymes tested, compound 1j displays selective inhibition of MMP-2, -9, and -12 with IC(50) values between 0.20 and 1.51 microuM, and in male golden Syrian hamsters, it shows protection against PPE-induced emphysema.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cricetinae
Isoenzymes / antagonists & inhibitors
Isoenzymes / chemistry
Keto Acids / chemical synthesis*
Keto Acids / chemistry
Keto Acids / pharmacology
Male
Matrix Metalloproteinase Inhibitors*
Matrix Metalloproteinases / chemistry
Mesocricetus
Models, Molecular
Pancreatic Elastase
Pulmonary Emphysema / chemically induced
Pulmonary Emphysema / enzymology
Pulmonary Emphysema / prevention & control*
Structure-Activity Relationship
Swine

Substances

Isoenzymes
Keto Acids
Matrix Metalloproteinase Inhibitors
Pancreatic Elastase
Matrix Metalloproteinases