Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 17, Issue 6, Pages 1538-1543Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2006.12.107
Keywords
carbonic anhydrase; cytosolic isozyme; tumor-associated isozyme IX; sulfonamide; hydroxamate; carboxylate; zinc-binding function
Categories
Ask authors/readers for more resources
The synthesis of a new class of sulfonamide carbonic anhydrase (CA, EC 4.2. 1. 1) inhibitors (CAIs), also possessing carboxylate/hydroxamate moieties in their molecule, is reported. These compounds may act on dual antitumor targets, the tumor-associated CA isozymes (CA IX) and some matrix metalloproteinases (MMPs). The compounds were prepared by an original method starting from iminodiacetic acid, and assayed as inhibitors of three isozymes, hCA I, II (cytosolic), and IX (transmembrane). The new derivatives showed weak inhibitory activity against isozyme I (K(I)s in the range of 95-8300 nM), were excellent to moderate CA II inhibitors (K(I)s in the range of 8.4-65 nM), and very good and selective CA IX inhibitors (Kis in the range of 3.8-26 nM). The primary sulfonamide moiety is a better zinc-binding group in the design of CAls as compared to the carboxylate/hydroxamate one, but the presence of hydroxamate functionalities in the molecule of CAls leads to selectivity for the tumor-associated isozyme IX over the ubiquitous, cytosolic isoform II. (c) 2007 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available