Synthesis of derivatives of methyl rosmarinate and their inhibitory activities against matrix metalloproteinase-1 (MMP-1)

Hu Yuan; Weiqiang Lu; Liyan Wang; Lei Shan; Honglin Li; Jin Huang; Qingyan Sun; Weidong Zhang

doi:10.1016/j.ejmech.2012.09.047

Synthesis of derivatives of methyl rosmarinate and their inhibitory activities against matrix metalloproteinase-1 (MMP-1)

Eur J Med Chem. 2013 Apr:62:148-57. doi: 10.1016/j.ejmech.2012.09.047. Epub 2012 Oct 16.

Authors

Hu Yuan¹, Weiqiang Lu, Liyan Wang, Lei Shan, Honglin Li, Jin Huang, Qingyan Sun, Weidong Zhang

Affiliation

¹ Department of Phytochemistry, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.

PMID: 23353736
DOI: 10.1016/j.ejmech.2012.09.047

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acrylates / chemical synthesis
Acrylates / chemistry
Acrylates / pharmacology*
Dose-Response Relationship, Drug
Drug Design
Humans
Matrix Metalloproteinase 1 / metabolism*
Matrix Metalloproteinase Inhibitors / chemical synthesis
Matrix Metalloproteinase Inhibitors / chemistry
Matrix Metalloproteinase Inhibitors / pharmacology*
Models, Molecular
Molecular Structure
Phenylpropionates / chemical synthesis
Phenylpropionates / chemistry
Phenylpropionates / pharmacology*
Structure-Activity Relationship

Substances

2-(3-(3,4-bis(benzyloxy)phenyl)acryloyloxy)-3-(3,4-dimethoxyphenyl)propanoic acid
Acrylates
Matrix Metalloproteinase Inhibitors
Phenylpropionates
Matrix Metalloproteinase 1