User menu

Accès à distance ? S'identifier sur le proxy UCLouvain

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

Primary tabs

Gérard, Estelle [UCL] Meulle, Aline [UCL] Feron, Olivier [UCL] Marchand-Brynaert, Jacqueline [UCL]

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.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2012
Language Anglais
Journal information "MedChemComm" - Vol. 3, no.2, p. 199-212 (2012)
Peer reviewed yes
Publisher RSC
issn 2040-2503
Publication status Publié
Affiliation UCL - SST/IMCN/MOST - Molecules, Solids and Reactivity
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
Links
  1. González-Amaro Roberto, Sánchez-Madrid Francisco, Drugs, inflammation and cell adhesion receptors, 10.1517/14656566.2.1.3
  2. Al-Turki D.A., Abou-Zeid L.A., Shehata I.A., Al-Omar M.A., Therapeutic and Toxic Effects of New NSAIDs and Related Compounds: A Review and Prospective Study, 10.3923/ijp.2010.813.825
  3. Rao Praveen P. N., Kabir Saad N., Mohamed Tarek, Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Progress in Small Molecule Drug Development, 10.3390/ph3051530
  4. Huang Zhangjian, Velázquez Carlos, Abdellatif Khaled, Chowdhury Morshed, Jain Sarthak, Reisz Julie, DuMond Jenna, King S. Bruce, Knaus Edward, Acyclic triaryl olefins possessing a sulfohydroxamic acid pharmacophore: synthesis, nitric oxide/nitroxyl release, cyclooxygenase inhibition, and anti-inflammatory studies, 10.1039/c005066k
  5. Bolger Joshua K., Tian Wen, Wolter William R., Cho Wonhwa, Suckow Mark A., Miller Marvin J., Synthesis and evaluation of 5-lipoxygenase translocation inhibitors from acylnitroso hetero-Diels–Alder cycloadducts, 10.1039/c0ob00714e
  6. Singh Palwinder, Mittal Anu, Kaur Satwinderjeet, Holzer Wolfgang, Kumar Subodh, 2, 3-Diaryl-5-ethylsulfanylmethyltetrahydrofurans as a new class of COX-2 inhibitors and cytotoxic agents, 10.1039/b803608j
  7. Dı́az-González Federico, Sánchez-Madrid Francisco, Inhibition of leukocyte adhesion: an alternative mechanism of action for anti-inflammatory drugs, 10.1016/s0167-5699(97)01216-4
  8. Tilley Jefferson W, Very late antigen-4 integrin antagonists, 10.1517/13543776.18.8.841
  9. Yang Ginger X., Hagmann William K., VLA-4 antagonists: Potent inhibitors of lymphocyte migration, 10.1002/med.10044
  10. DAVENPORT R, MUNDAY J, Alpha4-integrin antagonism — an effective approach for the treatment of inflammatory diseases?, 10.1016/j.drudis.2007.05.001
  11. P. Vanderslice and D. G.Woodside, in Progress in Respiratory Research, ed. T. T. Hansel and P. J. Barnes, Karger, Basel, 2010, vol. 39, pp. 169–173
  12. Vanderslice Peter, Woodside Darren G, Integrin antagonists as therapeutics for inflammatory diseases, 10.1517/13543784.15.10.1235
  13. Steinman Lawrence, Blocking adhesion molecules as therapy for multiple sclerosis: natalizumab, 10.1038/nrd1752
  14. Stüve Olaf, Bennett Jeffrey L., Pharmacological Properties, Toxicology and Scientific Rationale for the use of Natalizumab (Tysabri®) in Inflammatory Diseases, 10.1111/j.1527-3458.2007.00003.x
  15. Hemler Martin E., Elices Mariano J., Parker Christina, Takada Yoshikazu, Structure of the Integrin VLA-4 and its Cell-Cell and Cell-Matrix Adhesion Functions, 10.1111/j.1600-065x.1990.tb00561.x
  16. Stewart M, Leukocyte integrins, 10.1016/0955-0674(95)80111-1
  17. Barthel S. R., Johansson M. W., McNamee D. M., Mosher D. F., Roles of integrin activation in eosinophil function and the eosinophilic inflammation of asthma, 10.1189/jlb.0607344
  18. Elices Mariano J., Osborn Laurelee, Takada Yoshikazu, Crouse Carol, Luhowskyj Stefan, Hemler Martin E., Lobb Roy R., VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/Fibronectin binding site, 10.1016/0092-8674(90)90661-w
  19. Komoriya, J. Biol. Chem., 266, 15075 (1991)
  20. Battistini Lucia, Burreddu Paola, Carta Paola, Rassu Gloria, Auzzas Luciana, Curti Claudio, Zanardi Franca, Manzoni Leonardo, Araldi Elena M. V., Scolastico Carlo, Casiraghi Giovanni, 4-Aminoproline-based arginine-glycine-aspartate integrin binders with exposed ligation points: practical in-solution synthesis, conjugation and binding affinity evaluation, 10.1039/b914836a
  21. Štefanič Petra, Simončič Zvone, Breznik Matej, Plavec Janez, Anderluh Marko, Addicks Elisabeth, Giannis Athanassios, Kikelj Danijel, Conformationally tailored N-[(2-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl)carbonyl]proline templates as molecular tools for the design of peptidomimetics. Design and synthesis of fibrinogen receptor antagonists, 10.1039/b400490f
  22. Ruoslahti E, Pierschbacher M., New perspectives in cell adhesion: RGD and integrins, 10.1126/science.2821619
  23. Xiong J.-P., Crystal Structure of the Extracellular Segment of Integrin alpha Vbeta 3 in Complex with an Arg-Gly-Asp Ligand, 10.1126/science.1069040
  24. Lin Ko-Chung, Castro Alfredo C, Very late antigen 4 (VLA4) antagonists as anti-inflammatory agents, 10.1016/s1367-5931(98)80120-8
  25. Jackson David, Alpha 4 Integrin Antagonists, 10.2174/1381612023394737
  26. Macchiarulo, J. Chem. Inf. Comput. Sci., 44, 1829 (2004)
  27. Lin Ko-chung, Ateeq Humayun S., Hsiung Sherry H., Chong Lillian T., Zimmerman Craig N., Castro Alfredo, Lee Wen-cherng, Hammond Charles E., Kalkunte Sandhya, Chen Ling-Ling, Pepinsky R. Blake, Leone Diane R., Sprague Andrew G., Abraham William M., Gill Alan, Lobb Roy R., Adams Steven P., Selective, Tight-Binding Inhibitors of Integrin α4β1 That Inhibit Allergic Airway Responses, 10.1021/jm980673g
  28. Singh Juswinder, van Vlijmen Herman, Liao Yusheng, Lee Wen-Cherng, Cornebise Mark, Harris Mary, Shu I-hsiang, Gill Alan, Cuervo Julio H., Abraham William M., Adams Steven P., Identification of Potent and Novel α4β1 Antagonists Using in Silico Screening, 10.1021/jm020054e
  29. Momtaz Maryam, Rerat Vincent, Gharbi Sonia, Gérard Estelle, Pourcelle Vincent, Marchand-Brynaert Jacqueline, A graftable LDV peptidomimetic: Design, synthesis and application to a blood filtration membrane, 10.1016/j.bmcl.2007.12.006
  30. Kawada Kenji, Dolence E. Kurt, Morita Hiroyuki, Kometani Tadashi, Watt David S., Balapure Anil, Fitz Tony A., Orlicky David J., Gerschenson L. E., Prostaglandin photoaffinity probes: synthesis and biological activity of azide-substituted 16-phenoxy- and 17-phenyl-PGF2.alpha. prostaglandins, 10.1021/jm00121a046
  31. Abramovitch Rudolph A., Hawi Amale, Rodrigues J. Augusto R., Trombetta Tania R., Remote intramolecular functionalization of arylnitrenium ions. ipso-substitution and spiro-lactone formation, 10.1039/c39860000283
  32. Coste J., Le-Nguyen D., Castro B., PyBOP®: A new peptide coupling reagent devoid of toxic by-product, 10.1016/s0040-4039(00)94371-5
  33. Liu Ruiwu, Peng Li, Han Huijun, Lam Kit S., Structure–activity relationship studies of a series of peptidomimetic ligands for α4 β1 integrin on Jurkat T-leukemia cells, 10.1002/bip.20588
  34. Coluccini Carmine, Mazzanti Andrea, Pasini Dario, Locked chromophores as CD and NMR probes for the helical conformation of tetraamidic macrocycles, 10.1039/b924400j
  35. Chong Hyun-Soon, Song Hyun A., Dadwal Mamta, Sun Xiang, Sin Inseok, Chen Yunwei, Efficient Synthesis of Functionalized Aziridinium Salts, 10.1021/jo901893n
  36. Neises Bernhard, Steglich Wolfgang, Simple Method for the Esterification of Carboxylic Acids, 10.1002/anie.197805221
  37. Topliss John G., Utilization of operational schemes for analog synthesis in drug design, 10.1021/jm00280a002
  38. Chen Ling Ling, Whitty Adrian, Lobb Roy R., Adams Steven P., Pepinsky R. Blake, Multiple Activation States of Integrin α4β1Detected through Their Different Affinities for a Small Molecule Ligand, 10.1074/jbc.274.19.13167
Bibliographic reference Gérard, Estelle ; Meulle, Aline ; Feron, Olivier ; Marchand-Brynaert, Jacqueline. Diaryl urea LDV peptidomimetics as α 4β 1 integrin antagonists: Synthesis, adhesion inhibition and toxicity evaluation on CCRF-CEM cell line. In: MedChemComm, Vol. 3, no.2, p. 199-212 (2012)
Permanent URL http://hdl.handle.net/2078.1/124520