Topological virtual screening: a way to find new compounds active in ulcerative colitis by inhibiting NF-κB

Ulcerative colitis and Crohn's disease are chronic, immune-mediated inflammatory diseases of the gastrointestinal tract. Nuclear Factor KappaB(NF-kappa B) 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-kappa B. 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-kappa B 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.