title: 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.
authors.affiliation: Department of Pharmaceutical Technology, Meerut Institute of Engineering and Technology, Meerut 250005, India.
authors.forename: R K
authors.initials: RK
authors.lastname: Yadav
authors.forename: S P
authors.initials: SP
authors.lastname: Gupta
authors.forename: P K
authors.initials: PK
authors.lastname: Sharma
authors.forename: V M
authors.initials: VM
authors.lastname: Patil
mesh_terms: D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D008024:Ligands; D061965:Matrix Metalloproteinase Inhibitors; D013329:Structure-Activity Relationship; D015032:Zinc / Q000737:chemistry
chemical_list: D006877:Hydroxamic Acids; D008024:Ligands; D061965:Matrix Metalloproteinase Inhibitors; D015032:Zinc