Sulfonamide/sulfamate switch with a series of piperazinylureido derivatives: Synthesis, kinetic and in silico evaluation as carbonic anhydrase isoforms I, II, IV, and IX inhibitors.
Carbonic Anhydrase Inhibitors
/ chemical synthesis
Carbonic Anhydrases
/ metabolism
Dose-Response Relationship, Drug
Humans
Isoenzymes
/ antagonists & inhibitors
Molecular Docking Simulation
Molecular Structure
Piperazines
/ chemistry
Structure-Activity Relationship
Sulfonamides
/ chemistry
Sulfonic Acids
/ chemistry
Urea
/ analogs & derivatives
Antitumor
Bioisoster
Inhibitor
Metalloenzyme
Selectivity
Journal
European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510
Informations de publication
Date de publication:
15 Jan 2020
15 Jan 2020
Historique:
received:
16
10
2019
revised:
15
11
2019
accepted:
15
11
2019
pubmed:
1
12
2019
medline:
19
2
2020
entrez:
1
12
2019
Statut:
ppublish
Résumé
We report here a thorough structure-activity relationship (SAR) with piperazinylureido sulfamates as inhibitors of human (h) carbonic anhydrase (CA, EC 4.2.1.1). A SAR investigation over the structure of reported anti-cancer zinc-binder CAIs such as SLC-0111 and S4 was carried out by including the urea outer nitrogen atom into a substituted piperazine ring reducing the linker flexibility. The derivatives were assessed for the inhibition of CA I, II and IV (off-target isoforms) and the tumor-associated CA IX (anticancer drug target). CA I and IV were not effectively inhibited, whereas many low nanomolar inhibitors were evidenced against CA II (K
Identifiants
pubmed: 31784185
pii: S0223-5234(19)31048-7
doi: 10.1016/j.ejmech.2019.111896
pii:
doi:
Substances chimiques
Carbonic Anhydrase Inhibitors
0
Isoenzymes
0
Piperazines
0
Sulfonamides
0
Sulfonic Acids
0
Urea
8W8T17847W
sulfamic acid
9NFU33906Q
Carbonic Anhydrases
EC 4.2.1.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
111896Informations de copyright
Copyright © 2019 Elsevier Masson SAS. All rights reserved.