Design, synthesis and biological evaluation of ferulic Acid amides as selective matrix metalloproteinase inhibitors.
A series of ferulic acid amides with extended P1' groups were synthesized and tested for their inhibitory activities on matrix metalloproteinase (MMP)-1, MMP-2, and MMP-9. Preliminary structure-activity relationship analysis and docking studies indicated that ferulic acid amides with electron-donating groups at the amino phenyl ring showed better inhibitory activities and selectivity than those with electron-withdrawing groups. Compound 3e, which had a hydroxyl group at meta-position of amino phenyl ring, showed considerable inhibitory activities against MMP-2, MMP-9 and best selectivity over MMP-1. The findings of this study would provide information for the exploitation and utilization of ferulic acid as MMP inhibitor for metastatic tumor treatment.
Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, 138 Xianlin Road, 210046, Nanjing, Jiangsu, People's Republic of China. linianguang@njutcm.edu.cn; yupingtang@njutcm.edu.cn; dja@njutcm.edu.cn.
Zhi-Hao
ZH
Shi
Nian-Guang
NG
Li
Qian-Ping
QP
Shi
Hao-
H
Tang
Yu-Ping
YP
Tang
Wei-
W
Li
Lian-
L
Yin
Jian-Ping
JP
Yang
Jin-Ao
JA
Duan
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D003373:Coumaric Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D020128:Inhibitory Concentration 50; D061965:Matrix Metalloproteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D000577:Amides; D003373:Coumaric Acids; D061965:Matrix Metalloproteinase Inhibitors; C004999:ferulic acid; D020782:Matrix Metalloproteinases