Synthesis and discovery of (I-3,II-3)-biacacetin as a novel non-zinc binding inhibitor of MMP-2 and MMP-9

Pandurangan Nanjan; Jyotsna Nambiar; Bipin G Nair; Asoke Banerji

doi:10.1016/j.bmc.2015.03.084

Synthesis and discovery of (I-3,II-3)-biacacetin as a novel non-zinc binding inhibitor of MMP-2 and MMP-9

Bioorg Med Chem. 2015 Jul 1;23(13):3781-7. doi: 10.1016/j.bmc.2015.03.084. Epub 2015 Apr 9.

Authors

Pandurangan Nanjan¹, Jyotsna Nambiar¹, Bipin G Nair¹, Asoke Banerji²

Affiliations

¹ Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amrita University, Kollam, Kerala 690525, India.
² Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amrita University, Kollam, Kerala 690525, India. Electronic address: banerjiasoke@gmail.com.

PMID: 25907368
DOI: 10.1016/j.bmc.2015.03.084

Abstract

Eleven biflavones (7a-b and 9a-i) were synthesised by a simple and efficient protocol and screened for MMP-2 and MMP-9 inhibitory activities. Amongst them, a natural product-like analog, (I-3,II-3)-biacacetin (9h) was found to be the most potent inhibitor. Molecular docking studies suggest that unlike most of the known inhibitors, 9h inhibits MMP-2 and MMP-9 through non-zinc binding interactions.

Keywords: (I-3,II-3)-Biflavones; Biacacetin; Cerium ammonium nitrate (CAN); MMP-2 and MMP-9; Non-zinc binding inhibitor.

Publication types

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

MeSH terms

Binding Sites
Cell Survival / drug effects
Drug Discovery*
Flavones / chemical synthesis*
Flavones / pharmacology
Humans
Hydrogen Bonding
Matrix Metalloproteinase 2 / chemistry*
Matrix Metalloproteinase 2 / metabolism
Matrix Metalloproteinase 9 / chemistry*
Matrix Metalloproteinase 9 / metabolism
Matrix Metalloproteinase Inhibitors / chemical synthesis*
Matrix Metalloproteinase Inhibitors / pharmacology
Molecular Docking Simulation
Molecular Structure
Protein Binding
Protein Conformation

Substances

Flavones
Matrix Metalloproteinase Inhibitors
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
acacetin