Abstract
Nineteen natural compounds with diverse structures are identified as potential MMPIs using structure-based virtual screening from 4000 natural products. Hydroxycinnamic acid or analogs of natural products are important for potent inhibitory and selectivity against MMPs, and the solvent effect in the S1' pocket can affect the hydrophobic interactions and hydrogen bonds between MMPIs and MMPS, making MMPIs exhibit certain selectivity for a specific MMP isoenzyme. Furthermore, compound 5 can reduce the expression of both MMP-2 and active-MMP-9, and suppress the migration of MDA-MB-231 tumor cell in a wound healing assay, which may be further developed as an anticancer agent.
Copyright © 2012 Elsevier Ltd. All rights reserved.
MeSH terms
-
Amino Acid Sequence
-
Antineoplastic Agents / chemistry*
-
Antineoplastic Agents / pharmacology
-
Binding Sites
-
Biological Products / chemistry*
-
Biological Products / pharmacology
-
Cell Line, Tumor
-
Cell Movement / drug effects
-
Computer Simulation
-
Coumaric Acids / chemistry
-
Humans
-
Hydrogen Bonding
-
Hydrophobic and Hydrophilic Interactions
-
Matrix Metalloproteinase 2 / metabolism
-
Matrix Metalloproteinase 9 / metabolism
-
Matrix Metalloproteinase Inhibitors*
-
Matrix Metalloproteinases / metabolism
-
Molecular Sequence Data
-
Protease Inhibitors / chemistry*
-
Protease Inhibitors / pharmacology
-
Protein Structure, Tertiary
-
Sequence Alignment
-
Solvents / chemistry
Substances
-
Antineoplastic Agents
-
Biological Products
-
Coumaric Acids
-
Matrix Metalloproteinase Inhibitors
-
Protease Inhibitors
-
Solvents
-
Matrix Metalloproteinases
-
Matrix Metalloproteinase 2
-
Matrix Metalloproteinase 9