caa a22 4500 44587872X CHVBK 20180317145535.0 cr unu---uuuuu 170323e20111101xx s 000 0 eng 10.1007/s11030-011-9323-4 doi (NATIONALLICENCE)springer-10.1007/s11030-011-9323-4 Topological virtual screening: a way to find new compounds active in ulcerative colitis by inhibiting NF- κ B [Elektronische Daten] [María Gálvez-Llompart, María Recio, Ramón García-Domenech] Ulcerative colitis and Crohn's disease are chronic, immune-mediated inflammatory diseases of the gastrointestinal tract. Nuclear Factor Kappa B (NF-κB) is a transcription factor that plays a key role in regulating expression of multiple inflammatory and immune genes. In this study, a Topological Virtual Screening study has been carried out to achieve a model capable of finding new compounds active in ulcerative colitis by inhibiting NF-κB. Different topological indices were used as structural descriptors, and their relation to biological activity was determined using linear discriminant analysis. A topological model consisting of two discriminant functions was built up. The first function focused in the discrimination between NF-κB active and inactive compounds, and the second one in distinguishing between compounds active and inactive on ulcerative colitis. The model was then applied sequentially to a large database of compounds with unknown activity. Twenty-eight of such compounds were predicted to be active and selected for in vitro and in vivo testing. Springer Science+Business Media B.V., 2011 NF- κ B nationallicence Inflammatory bowel disease nationallicence Ulcerative colitis nationallicence Linear discriminant analysis nationallicence Molecular topology nationallicence NF- κ B : Nuclear factor kappa B nationallicence IBD : Inflammatory bowel disease nationallicence UC : Ulcerative colitis nationallicence CD : Crohn's disease nationallicence TNF- α : Tumor necrosis factor-α nationallicence IL : Interleukin nationallicence LDA : Linear discriminant analysis nationallicence HTS : High throughput screening nationallicence QSAR : Quantitative structure-activity relationship nationallicence DF : Discriminant function nationallicence TI : Topological indices nationallicence PDD : Pharmacological distribution diagram nationallicence Gálvez-Llompart María Molecular Connectivity and Drug Design Research Unit, Department of Physical Chemistry, Faculty of Pharmacy, University of Valencia, Avda. V.A. Estellés, s/n, 46100, Burjassot, Valencia, Spain aut Recio María Department of Pharmacology, Faculty of Pharmacy, University of Valencia, Burjassot, Valencia, Spain aut García-Domenech Ramón Molecular Connectivity and Drug Design Research Unit, Department of Physical Chemistry, Faculty of Pharmacy, University of Valencia, Avda. V.A. Estellés, s/n, 46100, Burjassot, Valencia, Spain aut Molecular Diversity Springer Netherlands 15/4(2011-11-01), 917-926 1381-1991 15:4<917 2011 15 11030 https://doi.org/10.1007/s11030-011-9323-4 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11030-011-9323-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Gálvez-Llompart María Molecular Connectivity and Drug Design Research Unit, Department of Physical Chemistry, Faculty of Pharmacy, University of Valencia, Avda. V.A. Estellés, s/n, 46100, Burjassot, Valencia, Spain aut NATIONALLICENCE 700 1- Recio María Department of Pharmacology, Faculty of Pharmacy, University of Valencia, Burjassot, Valencia, Spain aut NATIONALLICENCE 700 1- García-Domenech Ramón Molecular Connectivity and Drug Design Research Unit, Department of Physical Chemistry, Faculty of Pharmacy, University of Valencia, Avda. V.A. Estellés, s/n, 46100, Burjassot, Valencia, Spain aut NATIONALLICENCE 773 0- Molecular Diversity Springer Netherlands 15/4(2011-11-01), 917-926 1381-1991 15:4<917 2011 15 11030 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer