P035. New compounds against ulcerative colitis through molecular topology
M. Galvez-Llompart1, M. Recio2, R. Garcia-Domenech1
1University of Valencia, Department of Physical Chemistry, Burjassot (Valencia), Spain; 2University of Valencia, Department of Pharmacology, Burjassot (Valencia), Spain
Background: The QSAR based upon molecular topology, is a formalism built on describing the molecules by means of topological descriptors. This formalism has been used here to the search of active compounds against ulcerative colitis (UC). IL‑6 plays a key role in the uncontrolled intestinal inflammatory process .
Methods: Four compounds with potential activity versus UC were selected by our topological model . They were tested in vitro (Caco‑2 and RAW 264.7 cells) and in vivo (acute UC model induced by 5% dextran sulphate sodium (DSS)). Control group received no treatment. Products were orally administered (50 mg/kg) at days 0, 2, 4 and 7.
|Score||Weight loss||Stool consistency||Visible blood in feces|
Results: See Figures 1 and 2 and Table 2.
|Group||Weight loss||Stool consistency||Visible blood in feces||Total DAI score|
Conclusions: According to the results, 3 out of 4 compounds were able active in vitro, and 2 of them (Ro 410960 and DLT) had also been revealed as a preventive compounds in vivo.
1. Atreya, R.; Neurath, M. F. (2005), Involvement of IL‑6 in the pathogenesis of inflammatory bowel disease and colon cancer, Clin Rev Allerg Immu
2. Gálvez-Llompart, M.; Recio, M. C.; García-Domenech, R. (2011), Topological virtual screening: a way to find new compounds active in ulcerative colitis by inhibiting NF-kappaB., Mol. Divers
3. Recio, M. C.; Gálvez-Llompart, M.; Zanni, R; García-Domenech, R. (2011), New Inhibitors of Il‑6 Production In Caco‑2 Cells Through Molecular Topology Methodology, XXXIII Congreso de la Sociedad Española de Farmacología, Málaga (Spain).