Insertion of metal carbenes into the anilinic N-H bond of unprotected aminobenzenesulfonamides delivers low nanomolar inhibitors of human carbonic anhydrase IX and XII isoforms.
Aminobenzoates
/ chemistry
Antigens, Neoplasm
/ metabolism
Antineoplastic Agents
/ chemical synthesis
Carbonic Anhydrase IX
/ antagonists & inhibitors
Carbonic Anhydrase Inhibitors
/ chemical synthesis
Carbonic Anhydrases
/ metabolism
Cell Proliferation
/ drug effects
Coordination Complexes
/ chemical synthesis
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Isoenzymes
/ antagonists & inhibitors
Methane
/ analogs & derivatives
Molecular Structure
Structure-Activity Relationship
Sulfonamides
/ chemistry
Tumor Cells, Cultured
Cancer cells
Carbonic anhydrase
Diazo compounds
Enzyme inhibitors
Hypoxic environment
MTT-Test
Metal carbenes
Nanomolar inhibition
N–H insertion
Primary sulfonamides
Stopped-flow assay
The ‘SAFE’ protocol
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:
05 Jun 2021
05 Jun 2021
Historique:
received:
14
02
2021
revised:
01
03
2021
accepted:
01
03
2021
pubmed:
29
3
2021
medline:
7
8
2021
entrez:
28
3
2021
Statut:
ppublish
Résumé
Herein we report the synthesis of a set of thirty-four primary sulfonamides generated via formal N-H-insertion of metal carbenes into anilinic amino group of sulfanilamide and its meta-substituted analog. Obtained compounds were tested in vitro as inhibitors of four physiologically significant isoforms of the metalloenzyme human carbonic anhydrase (hCA, EC 4.2.1.1). Many of the synthesized sulfonamides displayed low nanomolar K
Identifiants
pubmed: 33774343
pii: S0223-5234(21)00201-4
doi: 10.1016/j.ejmech.2021.113352
pii:
doi:
Substances chimiques
Aminobenzoates
0
Antigens, Neoplasm
0
Antineoplastic Agents
0
Carbonic Anhydrase Inhibitors
0
Coordination Complexes
0
Isoenzymes
0
Sulfonamides
0
carbene
2465-56-7
CA9 protein, human
EC 4.2.1.1
Carbonic Anhydrase IX
EC 4.2.1.1
Carbonic Anhydrases
EC 4.2.1.1
carbonic anhydrase XII
EC 4.2.1.1
Methane
OP0UW79H66
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
113352Informations de copyright
Copyright © 2021 Elsevier Masson SAS. 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.