Synthesis of derivatives of methyl rosmarinate and their inhibitory activities against matrix metalloproteinase-1 (MMP-1).
A series of MMP-1 inhibitors have been identified based upon a methyl rosmarinate scaffold using structure-based drug design methods. The best compound in the series showed an IC50 value of 0.4 μM. A docking study was conducted for compound (S)-10n in order to investigate its binding interactions with MMP-1. The structure-activity relationships (SAR) were also briefly discussed. Useful SAR was established which provides important guidelines for the design of future generations of potent inhibitors against MMP-1.
Department of Phytochemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
Hu
H
Yuan
Weiqiang
W
Lu
Liyan
L
Wang
Lei
L
Shan
Honglin
H
Li
Jin
J
Huang
Qingyan
Q
Sun
Weidong
W
Zhang
D000179:Acrylates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D010666:Phenylpropionates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
C583778:2-(3-(3,4-bis(benzyloxy)phenyl)acryloyloxy)-3-(3,4-dimethoxyphenyl)propanoic acid; D000179:Acrylates; D061965:Matrix Metalloproteinase Inhibitors; D010666:Phenylpropionates; D020781:Matrix Metalloproteinase 1