Design and synthesis of MMP inhibitors with appended fluorescent tags for imaging and visualization of matrix metalloproteinase enzymes

John N Freskos; Bethel Asmelash; Kimberly R Gaston; Amol Karwa; Tim A Marzan; Maureen A Nickols; Thomas E Rogers; Tasha Schoenstein; Carolyn J Sympson; Bich Vu

doi:10.1016/j.bmcl.2013.08.050

Design and synthesis of MMP inhibitors with appended fluorescent tags for imaging and visualization of matrix metalloproteinase enzymes

Bioorg Med Chem Lett. 2013 Oct 15;23(20):5566-70. doi: 10.1016/j.bmcl.2013.08.050. Epub 2013 Aug 16.

Authors

John N Freskos¹, Bethel Asmelash, Kimberly R Gaston, Amol Karwa, Tim A Marzan, Maureen A Nickols, Thomas E Rogers, Tasha Schoenstein, Carolyn J Sympson, Bich Vu

Affiliation

¹ Department of Chemistry, Mallinckrodt Pharmaceuticals, 675 McDonnell Blvd., Hazelwood, MO 63042, United States. Electronic address: john.freskos@mallinckrodt.com.

PMID: 23999043
DOI: 10.1016/j.bmcl.2013.08.050

Abstract

We describe the synthesis, MMP-2 and 9 potency, and in vitro evaluation of a series of α-sulfone hydroxmate MMP inhibitors conjugated to a series of dyes with different absorption/emission lamina maxima's that can be used to visualize tumors.

Keywords: Imaging agents; MMP inhibitors; Tumor visualazation.

MeSH terms

Drug Design*
Fluorescent Dyes / chemistry*
Humans
MCF-7 Cells
Matrix Metalloproteinase 2 / chemistry
Matrix Metalloproteinase 2 / metabolism*
Matrix Metalloproteinase 9 / chemistry
Matrix Metalloproteinase 9 / metabolism*
Matrix Metalloproteinase Inhibitors / chemical synthesis*
Matrix Metalloproteinase Inhibitors / chemistry
Matrix Metalloproteinase Inhibitors / metabolism
Microscopy, Confocal

Substances

Fluorescent Dyes
Matrix Metalloproteinase Inhibitors
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9