Jump to main content
Jump to site search
Publishing
Advanced

Issue 6, 2015
Previous Article Next Article

Synthesis and biological evaluation of potential small moleculeinhibitors of tumor necrosis factor†

Christos Papaneophytou,ab   Polyxeni Alexiou,c   Athanasios Papakyriakou,d   Evangelos Ntougkos,e   Katerina Tsiliouka,f   Anna Maranti,f   Fotini Liepouri,f   Alexandros Strongilos,f   Anthi Mettou,ab   Elias Couladouros,c   Elias Eliopoulos,d   Eleni Douni,de   George Kolliase  and  George Kontopidis*ab  
Author affiliations

* Corresponding authors

a Department of Biochemistry, Veterinary School, University of Thessaly, Trikalon 224, Karditsa 43100, Greece
E-mail: gkontopidis@vet.uth.gr
Fax: +30 24410 66041
Tel: +30 24410 66081

b Institute for Research and Technology of Thessaly (I.RE.TE.TH.), The Centre for Research & Technology Hellas (CE.R.TH.), Dimitriados 95 & Paulou Mela, Volos 38333, Greece

c Laboratory of General Chemistry, Department of Science, Agricultural University of Athens, Iera Odos 75, Athens 11855, Greece

d Laboratory of Genetics, Department of Biotechnology, Agricultural University of Athens, Iera Odos 75, Athens 11855, Greece

e Biomedical Sciences Research Center “Alexander Fleming”, Vari, Greece

f pro-ACTINA S.A., Archimidous Str. 59, P.O.Box 205, Koropi, Athens 19400, Greece

Abstract

Inhibition of tumor necrosis factor (TNF) production or function by small molecules has become a major focus in the pharmaceutical industry for the treatment of rheumatoid arthritis. In this study, a series of 39 novel SPD-304 analogs were designed, synthesized and evaluated as TNFinhibitors. Our results show that small structural changes produce ligands with similar binding affinities (Kd) for TNF, but significantly different potencies in a L929 cell-based assay. In addition, contrary to the high affinity of compounds 4e, 8c and 10e for TNF in vitro, the potency of these compounds was determined to be low. We propose that these differences can partly be explained by the physicochemical characteristics of the synthesized SPD-304 analogs. Our findings were supplemented by molecular docking studies on the TNF dimer. These synthesized analogs may serve as a starting point for developing novel TNF inhibitors.

Graphical abstract: Synthesis and biological evaluation of potential small molecule inhibitors of tumor necrosis factor

Back to tab navigation
Download options Please wait...

Supplementary files

Article information

https://doi.org/10.1039/C5MD00023H
Submitted
18 Jan 2015
Accepted
18 May 2015
First published
19 May 2015
Med. Chem. Commun., 2015,6, 1196-1209
Article type
Concise Article
Author version available
Download author version (PDF)
Permissions
Request permissions

Synthesis and biological evaluation of potential small moleculeinhibitors of tumor necrosis factor

C. Papaneophytou, P. Alexiou, A. Papakyriakou, E. Ntougkos, K. Tsiliouka, A. Maranti, F. Liepouri, A. Strongilos, A. Mettou, E. Couladouros, E. Eliopoulos, E. Douni, G. Kollias and G. Kontopidis, Med. Chem. Commun., 2015, 6, 1196
DOI: 10.1039/C5MD00023H

If you are not the author of this article and you wish to reproduce material from it in a third party non-RSC publication you must formally request permission using Copyright Clearance Center. Go to our Instructions for using Copyright Clearance Center page for details.

Authors contributing to RSC publications (journal articles, books or book chapters) do not need to formally request permission to reproduce material contained in this article provided that the correct acknowledgement is given with the reproduced material.

Reproduced material should be attributed as follows:

  • For reproduction of material from NJC:
    Reproduced from Ref. XX with permission from the Centre National de la Recherche Scientifique (CNRS) and The Royal Society of Chemistry.
  • For reproduction of material from PCCP:
    Reproduced from Ref. XX with permission from the PCCP Owner Societies.
  • For reproduction of material from PPS:
    Reproduced from Ref. XX with permission from the European Society for Photobiology, the European Photochemistry Association, and The Royal Society of Chemistry.
  • For reproduction of material from all other RSC journals and books:
    Reproduced from Ref. XX with permission from The Royal Society of Chemistry.

If the material has been adapted instead of reproduced from the original RSC publication "Reproduced from" can be substituted with "Adapted from".

In all cases the Ref. XX is the XXth reference in the list of references.

If you are the author of this article you do not need to formally request permission to reproduce figures, diagrams etc. contained in this article in third party publications or in a thesis or dissertation provided that the correct acknowledgement is given with the reproduced material.

Reproduced material should be attributed as follows:

  • For reproduction of material from NJC:
    [Original citation] - Reproduced by permission of The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC
  • For reproduction of material from PCCP:
    [Original citation] - Reproduced by permission of the PCCP Owner Societies
  • For reproduction of material from PPS:
    [Original citation] - Reproduced by permission of The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC
  • For reproduction of material from all other RSC journals:
    [Original citation] - Reproduced by permission of The Royal Society of Chemistry

If you are the author of this article you still need to obtain permission to reproduce the whole article in a third party publication with the exception of reproduction of the whole article in a thesis or dissertation.

Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.

Search articles by author

Spotlight

Advertisements