Selective inhibition of matrix metalloproteinase isozymes and in vivo protection against emphysema by substituted gamma-keto carboxylic acids.
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.
Ma
Dawei
D
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
Jiang
Yongwen
Y
Chen
Fangping
F
Gong
Li-kun
LK
Ding
Ke
K
Xu
Yong
Y
Wang
Renxiao
R
Ge
Aihua
A
Ren
Jin
J
Li
Jingya
J
Li
Jia
J
Ye
Qizhuang
Q
D000818:Animals; D006224:Cricetinae; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry; D007651:Keto Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000737:chemistry; D008647:Mesocricetus; D008958:Models, Molecular; D010196:Pancreatic Elastase; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D013329:Structure-Activity Relationship; D013552:Swine
D007527:Isoenzymes; D007651:Keto Acids; D061965:Matrix Metalloproteinase Inhibitors; D010196:Pancreatic Elastase; D020782:Matrix Metalloproteinases