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

Murat Bozdag; Giulio Poli; Andrea Angeli; Elena Lucarini; Tiziano Tuccinardi; Lorenzo Di Cesare Mannelli; Silvia Selleri; Carla Ghelardini; Jean-Yves Winum; Fabrizio Carta; Claudiu Supuran

doi:10.1016/j.bioorg.2019.103033

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

Journal article

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

Murat Bozdag, Giulio Poli, Andrea Angeli, Elena Lucarini, Tiziano Tuccinardi, Lorenzo Di Cesare Mannelli, Silvia Selleri, Carla Ghelardini, Jean-Yves Winum, Fabrizio Carta, …

Bioorganic Chemistry, Vol.89

08/2019

DOI: https://doi.org/10.1016/j.bioorg.2019.103033

Abstract

Carbonic Anhydrase

Neuropathic pain

Carbonic Anhydrase Inhibitors

N-aryl-N’-ureido-O-sulfamates

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 KI s 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.

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Title: N-aryl-N’-ureido-O-sulfamates: Potent and selective inhibitors of the human Carbonic Anhydrase VII isoform with neuropathic pain relieving properties
Creators - without role: Murat Bozdag - University of Florence
Giulio Poli - University of Pisa
Andrea Angeli - University of Florence
Elena Lucarini - University of Florence
Tiziano Tuccinardi - University of Pisa
Lorenzo Di Cesare Mannelli - University of Florence
Silvia Selleri - University of Florence
Carla Ghelardini - University of Florence
Jean-Yves Winum - Université de Montpellier, Institut des Biomolécules Max Mousseron - IBMM
Fabrizio Carta - University of Florence
Claudiu Supuran - University of Florence
Publication Details: Bioorganic Chemistry, Vol.89
Identifiers: 9943152309311
Academic Unit: Institut des Biomolécules Max Mousseron - IBMM
Language: English
Resource Type: Journal article
Local Fields: hal-03527057