A combinatorial approach for the discovery of drug-like inhibitors of 15-lipoxygenase-1.
15-Lipoxygenase-1
Acylhydrazone
Combinatorial chemistry
Screening
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 Jul 2019
15 Jul 2019
Historique:
received:
19
12
2018
revised:
02
04
2019
accepted:
09
04
2019
pubmed:
27
4
2019
medline:
18
6
2019
entrez:
27
4
2019
Statut:
ppublish
Résumé
Human 15-lipoxygenase-1 (15-LOX-1) is a mammalian lipoxygenase which plays an important regulatory role in several CNS and inflammatory lung diseases. To further explore the role of this enzyme in drug discovery, novel potent inhibitors with favorable physicochemical properties are required. In order to identify such new inhibitors, we established a combinatorial screening method based on acylhydrazone chemistry. This represents a novel application of combinatorial chemistry focusing on the improvement of physicochemical properties, rather than on potency. This strategy allowed us to efficiently screen 44 reaction mixtures of different hydrazides and our previously reported indole aldehyde core structure, without the need for individual synthesis of all possible combinations of building blocks. Our approach afforded three new inhibitors with IC
Identifiants
pubmed: 31026746
pii: S0223-5234(19)30327-7
doi: 10.1016/j.ejmech.2019.04.021
pii:
doi:
Substances chimiques
Hydrazones
0
Indoles
0
Ligands
0
Lipoxygenase Inhibitors
0
ALOX15 protein, human
EC 1.13.11.33
Arachidonate 15-Lipoxygenase
EC 1.13.11.33
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
45-55Informations de copyright
Copyright © 2019 Elsevier Masson SAS. All rights reserved.