Molecular Diversity

, Volume 17, Issue 3, pp 573–593 | Cite as

Novel potential agents for ulcerative colitis by molecular topology: suppression of IL-6 production in Caco-2 and RAW 264.7 cell lines

  • María Galvez-Llompart
  • María del Carmen Recio Iglesias
  • Jorge Gálvez
  • Ramón García-Domenech
Full-Length Paper


Ulcerative colitis (UC) is an immune-mediated chronic and relapsing intestinal inflammatory disease. Interleukin (IL)-6, a pro-inflammatory cytokine, plays a key role in the uncontrolled intestinal inflammatory process, which is a main characteristic of UC. In this work, a quantitative structure–activity relationship model based on molecular topology (MT) has been built up to predict the IL-6 mediated anti-UC activity. After an external validation of the model, a virtual screening of the MicroSource Pure Natural Products Collection and Sigma-Aldrich databases was carried out looking for potential new active compounds. From the entire set of compounds labeled as active by the model, four of them, namely alizarin-3-methylimino-N,N-diacetic acid (AMA), Calcein, (+)-dibenzyl-l-tartrate (DLT), and Ro 41-0960, were tested in vitro by determination of IL-6 production in two cell lines (RAW 264.7 and Caco-2). The results demonstrate that three of them were able to significantly reduce IL-6 levels in both cell lines and particularly one, namely Ro 41-0960. These results confirm MT’s efficacy as a tool for the selection of compounds potentially active in UC.

Graphical Abstract


Interleukin-6 (IL-6) Quantitative structure–activity relationship (QSAR) Molecular topology Virtual screening RAW 264.7 (mouse leukemic monocyte macrophage cell line) Caco-2 (human epithelial colorectal adenocarcinoma cells) 



We thank the Ministerio de Economia y Competitividad, Spain (projects SAF2009-13059-C03-01 and SAF2009-13059-C03-02) for support of this study. M Galvez-Llompart acknowledges the Atraccio de talents Fellowship provided by the University of Valencia to carry out this study.

Supplementary material

11030_2013_9458_MOESM1_ESM.doc (210 kb)
Supplementary material 1 (doc 210 KB)


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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • María Galvez-Llompart
    • 1
  • María del Carmen Recio Iglesias
    • 2
  • Jorge Gálvez
    • 1
  • Ramón García-Domenech
    • 1
  1. 1.Molecular Connectivity & Drug Design Research Unit, Department of Physical Chemistry, Faculty of PharmacyUniversity of ValenciaValenciaSpain
  2. 2.Department of Pharmacology, Faculty of PharmacyUniversity of ValenciaValenciaSpain

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