N-aryl-N'-ureido-O-sulfamates as potent and selective inhibitors of hCA VB over hCA VA: Deciphering the binding mode of new potential agents in mitochondrial dysfunctions.
Carbonic Anhydrase Inhibitors
/ chemistry
Carbonic Anhydrases
/ metabolism
Humans
Mitochondria
/ drug effects
Mitochondrial Proteins
/ antagonists & inhibitors
Molecular Docking Simulation
Protein Isoforms
/ antagonists & inhibitors
Structure-Activity Relationship
Sulfonic Acids
/ chemistry
Urea
/ analogs & derivatives
Carbonic anhydrase
Carbonic anhydrase inhibitors
Mitochondrial CAs
Mitochondrial dynamics
N-Aryl-N′-ureido-O-sulfamates
Obesity
Selectivity
Journal
Bioorganic chemistry
ISSN: 1090-2120
Titre abrégé: Bioorg Chem
Pays: United States
ID NLM: 1303703
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
received:
28
03
2020
revised:
19
04
2020
accepted:
28
04
2020
pubmed:
16
5
2020
medline:
4
3
2021
entrez:
16
5
2020
Statut:
ppublish
Résumé
N-aryl-N'-ureido-O-sulfamates (AUSs) were recently reported as new class of Carbonic Anhydrase Inhibitors (CAIs), endowed of high potency and selectivity against hCA VII and XII. In this work, we extended the investigational study on this new class of CAIs profiling them against the mitochondrial CA isoforms hCA VA and VB. The results revealed a very interesting selectivity profile, with dramatic selectivity against hCA VB over the VA isoform observed for all the analyzed compounds 2-22. On derivative 15, selected as one of the most promising among the series, molecular modeling studies were conducted, highlighting the importance of small residue substitution between the two isoforms in substantially changing the tail orientation and interaction with the enzymes.
Identifiants
pubmed: 32413627
pii: S0045-2068(20)30708-2
doi: 10.1016/j.bioorg.2020.103896
pii:
doi:
Substances chimiques
Carbonic Anhydrase Inhibitors
0
Mitochondrial Proteins
0
Protein Isoforms
0
Sulfonic Acids
0
Urea
8W8T17847W
sulfamic acid
9NFU33906Q
Carbonic Anhydrases
EC 4.2.1.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
103896Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.