[Design, synthesis and activity evaluation of novel matrix metalloproteinases inhibitors based on the structure of enzyme].
A novel inhibitor series for matrix metalloproteinases (MMPs) were designed and synthesized. Using succinate and malonate as zinc binding groups and long hydrophobic substituents to bind with S1' pockets, the compounds showed micromolar inhibition and selectivity for MMP-2 over others. And we found a better activity compound. It is a chance to find a better precursor of MMP-2 inhibitors with activity and bioavailability by further optimization of compounds.
Jia
Hong
H
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union'Medical College, Beijing 100050, China.
Guo
Yan-shen
YS
Ge
Yi-yu
YY
Wen
Hui
H
Yang
Jing
J
Yang
Xiu-ying
XY
Du
Guan-hua
GH
Yang
Guang-zhong
GZ
D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases