N-aryl-N'-ureido-O-sulfamates: Potent and selective inhibitors of the human Carbonic Anhydrase VII isoform with neuropathic pain relieving properties.

Abstract

Herein we report for the first time an efficient synthetic procedure for the preparation of N-aryl-N'-ureido-O-sulfamates (AUSs) as a new class of Carbonic Anhydrase Inhibitors (CAIs). The compounds were tested for the inhibition of several human (h) Carbonic Anhydrase (CA; EC 4.2.1.1) isoforms. Interesting inhibition activity and high selectivity against CA VII and XII versus CA I and II, with KIs in the low nanomolar range, were observed. Molecular modeling studies allowed us to decipher the structural features underpinning the selective inhibitory profile of AUSs towards isoforms CAs VII and XII. A selection of sulfamates showed promising neuropathic pain modulating effects in an in vivo animal model of oxaliplatin induced pain.

• Authors: Murat Bozdag, Giulio Poli, Andrea Angeli, Elena Lucarini, Tiziano Tuccinardi, Lorenzo Di Cesare Mannelli, Silvia Selleri, Carla Ghelardini, Jean-Yves Winum, Fabrizio Carta, Claudiu T Supuran
• Journal: Bioorganic chemistry (Bioorg Chem) Vol. 89 Pg. 103033 (08 2019) ISSN: 1090-2120 [Electronic] United States
• PMID: 31212085 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Carbonic Anhydrase Inhibitors
• Isoenzymes
• Phenylurea Compounds
• Oxaliplatin
• Carbonic Anhydrases
• carbonic anhydrase VI

Topics

• Animals
• Carbonic Anhydrase Inhibitors (chemical synthesis, chemistry, pharmacology)
• Carbonic Anhydrases (metabolism)
• Dose-Response Relationship, Drug
• Drug Design
• Humans
• Isoenzymes (antagonists & inhibitors, metabolism)
• Male
• Mice
• Models, Molecular
• Molecular Structure
• Neuralgia (chemically induced, drug therapy, pathology)
• Oxaliplatin
• Pain Measurement
• Phenylurea Compounds (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship