title: Novel potential agents for ulcerative colitis by molecular topology: suppression of IL-6 production in Caco-2 and RAW 264.7 cell lines.
abstract: 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.
authors.affiliation: Molecular Connectivity & Drug Design Research Unit, Department of Physical Chemistry, Faculty of Pharmacy, University of Valencia, Avenida V.A. Estelles s/n, Burjasot, 46100 , Valencia, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Galvez-Llompart
authors.forename: María
authors.initials: M
authors.lastname: Del Carmen Recio Iglesias
authors.forename: Jorge
authors.initials: J
authors.lastname: Gálvez
authors.forename: Ramón
authors.initials: R
authors.lastname: García-Domenech
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D001577:Benzophenones / Q000737:chemistry; D018938:Caco-2 Cells; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D004353:Drug Evaluation, Preclinical; D005452:Fluoresceins / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001577:Benzophenones; D005452:Fluoresceins; D005456:Fluorescent Dyes; D015850:Interleukin-6; C071721:Ro 41-0960; C007740:fluorexon