Design, synthesis and biological evaluation of low molecular weight CXCR4 ligands.
Anti-HIV
Azamacrocyclic compound
CXCR4-binding
Dipicolylamine
NanoBRET assay
Journal
Bioorganic & medicinal chemistry
ISSN: 1464-3391
Titre abrégé: Bioorg Med Chem
Pays: England
ID NLM: 9413298
Informations de publication
Date de publication:
15 03 2019
15 03 2019
Historique:
received:
31
12
2018
revised:
01
02
2019
accepted:
05
02
2019
pubmed:
18
2
2019
medline:
16
1
2020
entrez:
18
2
2019
Statut:
ppublish
Résumé
The chemokine receptor CXCR4/stromal cell-derived factor-1 (SDF-1: CXCL12) signaling axis represents a crucial drug target due to its relevance to several diseases such as HIV-1 infection, cancer, leukemia, and rheumatoid arthritis. With the aim of enhancing the binding affinity and anti-HIV activity of a potent CXCR4 ligand as a lead, 23 low molecular weight compounds containing dipicolylamine (Dpa) and cyclam cationic moieties with varying spacers and spatial positioning were designed, synthesized and biologically evaluated. All of the synthesized compounds screened at 1.0 μM in the NanoBRET assay system exhibited >70% inhibition of the binding of a competitive probe TAMRA-Ac-TZ14011 (10 nM) to CXCR4 in the presence of zinc (II) ion. Furthermore, selected compounds 3, 8, 9, 19 and 21 with spatial distances between the next carbon to Dpa and the next carbon to cyclam within the range of 6.5-7.5 Å showed potent binding affinity selective for CXCR4 with IC
Identifiants
pubmed: 30772128
pii: S0968-0896(18)32183-7
doi: 10.1016/j.bmc.2019.02.013
pii:
doi:
Substances chimiques
2,2'-dipicolylamine
0
Amines
0
Anti-HIV Agents
0
CXCR4 protein, human
0
Heterocyclic Compounds
0
Ligands
0
Picolinic Acids
0
Receptors, CXCR4
0
cyclam
295-37-4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1130-1138Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.