Natural products as a gold mine for selective matrix metalloproteinases inhibitors.
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.
Shanghai Key Laboratory of New Drug Design, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
Liyan
L
Wang
Xi
X
Li
Shoude
S
Zhang
Weiqiang
W
Lu
Sha
S
Liao
Xiaofeng
X
Liu
Lei
L
Shan
Xu
X
Shen
Hualiang
H
Jiang
Weidong
W
Zhang
Jin
J
Huang
Honglin
H
Li
D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D001688:Biological Products / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D003198:Computer Simulation; D003373:Coumaric Acids / Q000737:chemistry; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008969:Molecular Sequence Data; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D012997:Solvents / Q000737:chemistry
D000970:Antineoplastic Agents; D001688:Biological Products; D003373:Coumaric Acids; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D012997:Solvents; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9