title: Selective inhibition of matrix metalloproteinase isozymes and in vivo protection against emphysema by substituted gamma-keto carboxylic acids.
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.
authors.affiliation: 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
authors.forename: Dawei
authors.initials: D
authors.lastname: Ma
authors.forename: Yongwen
authors.initials: Y
authors.lastname: Jiang
authors.forename: Fangping
authors.initials: F
authors.lastname: Chen
authors.forename: Li-kun
authors.initials: LK
authors.lastname: Gong
authors.forename: Ke
authors.initials: K
authors.lastname: Ding
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.forename: Renxiao
authors.initials: R
authors.lastname: Wang
authors.forename: Aihua
authors.initials: A
authors.lastname: Ge
authors.forename: Jin
authors.initials: J
authors.lastname: Ren
authors.forename: Jingya
authors.initials: J
authors.lastname: Li
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Qizhuang
authors.initials: Q
authors.lastname: Ye
mesh_terms: 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
chemical_list: D007527:Isoenzymes; D007651:Keto Acids; D061965:Matrix Metalloproteinase Inhibitors; D010196:Pancreatic Elastase; D020782:Matrix Metalloproteinases