Recent advances in studies on hydroxamates as matrix metalloproteinase inhibitors: a review.

Abstract:

:Matrix metalloproteinases (MMPs) are a large family of calcium-dependent zinc- containing endopeptidases, which are responsible for the tissue remodeling and degradation of the extracellular matrix (ECM), including collagens, elastins, gelatin, matrix glycoproteins, and proteoglycan. The inappropriate expression of these MMPs constitutes part of the pathogenic mechanism in several diseases, therefore they are subject to inhibition. They can be inhibited by endogenous proteinase inhibitors such as 2-macroglobulin or by the family of tissue inhibitors of metalloproteinases (TIMPs), which are glycoproteins of molecular weight 21-30 kDa, consisting of 184-194 amino acid residues. Recently, many different classes of synthetic inhibitors have been developed in which the hydroxamic acidbased class of compounds (hydroxamates) have been most widely studied, as their hydroxamic acid group (CONHOH) enables them to act as a bidentate ligand with the zinc ion present in MMPs, leading to much stronger interaction with the receptor as compared to any other class of inhibitors. The present review describes in detail the recent development on this class of MMP inihibitors. Compounds like 12,17e, f, g and h, 45j, 45k, 50f, 62a, 63a, and 63b have been reported to be highly promising for further development.

journal_name

Curr Med Chem

authors

Yadav RK,Gupta SP,Sharma PK,Patil VM

doi

10.2174/092986711795471329

subject

Has Abstract

pub_date

2011-01-01 00:00:00

pages

1704-22

issue

11

eissn

0929-8673

issn

1875-533X

pii

BSP/CMC/E-Pub/2011/ 113

journal_volume

18

pub_type

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