Diaryl urea LDV peptidomimetics as α 4β 1 integrin antagonists: Synthesis, adhesion inhibition and toxicity evaluation on CCRF-CEM cell line

Gérard, Estelle; Meulle, Aline; Feron, Olivier; Marchand-Brynaert, Jacqueline

doi:10.1039/c1md00229e

Diaryl urea LDV peptidomimetics as α 4β 1 integrin antagonists: Synthesis, adhesion inhibition and toxicity evaluation on CCRF-CEM cell line

Gérard, Estelle

;

Meulle, Aline

;

Feron, Olivier

;

Marchand-Brynaert, Jacqueline

(2012) MedChemComm — Vol. 3, n° 2, p. 199-212 (2012)

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Authors

Gérard, EstelleUCLouvain
Author
Meulle, AlineUCLouvain
Author
Feron, OlivierUCLouvain
Author
Marchand-Brynaert, JacquelineUCLouvain
Author

Abstract

The α 4β 1 (VLA-4) integrin plays an important role in the leukocytes migration to sites of inflammation and has been validated as a therapeutic target for treating inflammatory diseases. Two families of regioisomeric peptidomimetics based on the Leu-Asp-Val (LDV) motif recognized by the α 4β 1 integrin were synthesized. Their activity was evaluated through cell adhesion and cell detachment assays using the CCRF-CEM cell line (Human T cells lymphoblast-like). Among the 20 antagonists tested, 17 appeared to be a good inhibitor of the adhesion of CCRF-CEM to fibronectin with an IC 50 value of 24 μM, comparable to the reference LDV peptide derivative 2. The toxicity of the peptidomimetics was also controlled. © 2012 The Royal Society of Chemistry.

Affiliations

UCLouvainSST/IMCN/MOST - Molecular Chemistry, Materials and Catalysis

Citations

APA
Chicago
FWB

Gérard, E., Meulle, A., Feron, O., & Marchand-Brynaert, J. (2012). Diaryl urea LDV peptidomimetics as α 4β 1 integrin antagonists: Synthesis, adhesion inhibition and toxicity evaluation on CCRF-CEM cell line. MedChemComm, 3(2), 199-212. https://doi.org/10.1039/c1md00229e (Original work published 2012)

Publication type

Journal articleResearch article

Year

2012

Language

English

Handle

https://hdl.handle.net/2078.5/93891

DOI

10.1039/c1md00229e

Serial

MedChemComm

Volume: 3 Issue: 2 Pages: 199-212 Date: 2012 ISSN: 2040-2503 eISSN: 2040-2511

Publisher

RSC

Cambridge

Peer-reviewed

Yes

Publication status

Published

Keywords

2 phenylethyl 3 [2 (2 tert butoxy 2 oxoethoxy) 5 [[[4 [[(2,6 dimethylphenyl)carbamoyl]amino]phenyl]acetyl]amino]phenyl]propanoate
[2 [3 (benzyloxy) 3 oxopropyl] 4 [[[4 [[[2 (trifluoromethyl)phenyl]carbamoyl]amino]phenyl]acetyl]amino]phenoxy]acetic acid
[2 [3 [(4 chlorobenzyl)oxyl] 3 oxopropyl] 4 [[[4 [[(2,6 dimethylphenyl)carbamoyl]amino]phenyl]acetyl]amino]phenoxy]acetic acid
[4 [[[4 [[(2,6 dimethylphenyl)carbamoyl]amino]phenyl]acetyl]amino] 2 [3 oxo 3 (2 phenylethoxy)propyl]phenoxy]acetic acid
[4 [[[4 [[(2,6 dimethylphenyl)carbamoyl]amino]phenyl]acetyl]amino] 2 [3 oxo 3 [(2 phenylethyl)amino]propyl]phenoxy]acetic acid
Benzyl 3 [2 (2 tert butoxy 2 oxoethoxy) 5 [[[4 [[[2 (trifluoromethyl)phenyl]carbamoyl]amino]phenyl]acetyl]amino]phenyl]propanoate
Benzyl 3 [2 hydroxy 5 [[[4 [[[2 (trifluoromethyl)phenyl]carbamoyl]amino]phenyl]acetyl]amino]phenyl]propanoate
Benzyl 3 [5 [[[4 [[(2,6 dimethylphenyl)carbamoyl]amino]phenyl]acetyl]amino] 2 hydroxyphenyl]propanoate
Diarylurea leucylaspartylvalyl peptidomimetic
Fibronectin
Methyl 3 [2 hydroxy 5 [[[4 [[[2 (trifluoromethyl)phenyl]carbamoyl]amino]phenyl]acetyl]amino]phenyl]propanoate
3 [2 (2 tert butoxy 2 oxoethoxy) 5 [[[4 [[(2,6 dimethylphenyl)carbamoyl]amino]phenyl]acetyl]amino]phenyl]propanoic acid
Methyl 3 [5 [[[4 [[(2,6 dimethylphenyl)carbamoyl]amino]phenyl]acetyl]amino] 2 hydroxyphenyl]propanoate
Peptidomimetic agent
Tert butyl[2 [3 (benzylamino) 3 oxopropyl] 4 [[[4 [[(2,6 dimethylphenyl)carbamoyl]amino]phenyl]acetyl]amino]phenoxy]acetate
Tert butyl[4 [[[4 [[(2,6 dimethylphenyl)carbamoyl]amino]phenyl]acetyl]amino]phenoxy]acetate
Unclassified drug
Very late activation antigen 4
Article
Cell adhesion
Cell assay
Cell detachment assay
3 [2 (2 tert butoxy 2 oxoethoxy) 5 [[[4 [[[2 (trifluoromethyl)phenyl]carbamoyl]amino]phenyl]acetyl]amino]phenyl]propanoate
Cell line
Chemical modification
Concentration response
Controlled study
Deprotection reaction
Drug activity
Drug design
Drug structure
Drug synthesis
Esterification
3 [2 hydroxy 5 [[[4 [[[2 (trifluoromethyl)phenyl]carbamoyl]amino]phenyl]acetyl]amino]phenyl]propanoic acid
Human
Human cell
Hydrogenation
IC 50
Peptide synthesis
Priority journal
Protein motif
3 [5 [[[4 [[(2,6 dimethylphenyl)carbamoyl]amino]phenyl]acetyl]amino] 2 hydroxyphenyl]propanoic acid
3[2 (carboxymethoxy) 5 [[[4 [[(2,6 dimethylphenyl)carbamoyl]amino]phenyl]acetyl]amino]phenyl]propanoic acid
4 chlorobenzyl 3 [2 (2 tert butoxy 2 oxoethoxy) 5 [[[4 [[(2,6 dimethylphenyl)carbamoyl]amino]phenyl]acetyl]amino]phenyl]propanoate
[2 [3 (benzylamino) 3 oxopropyl] 4 [[[4 [[(2,6 dimethylphenyl)carbamoyl]amino]phenyl]acetyl]amino]phenoxy]acetic acid
[2 [3 (benzyloxy) 3 oxopropyl] 4 [[[4 [[(2,6 dimethylphenyl)carbamoyl]amino]phenyl]acetyl]amino]phenoxy]acetic acid