title: Docking of molecules identified in bioactive medicinal plants extracts into the p50 NF-kappaB transcription factor: correlation with inhibition of NF-kappaB/DNA interactions and inhibitory effects on IL-8 gene expression.
abstract: BACKGROUND
  The transcription factor NF-kappaB is a very interesting target molecule for the design on anti-tumor, anti-inflammatory and pro-apoptotic drugs. However, the application of the widely-used molecular docking computational method for the virtual screening of chemical libraries on NF-kappaB is not yet reported in literature. Docking studies on a dataset of 27 molecules from extracts of two different medicinal plants to NF-kappaB-p50 were performed with the purpose of developing a docking protocol fit for the target under study.
  
  
  RESULTS
  We enhanced the simple docking procedure by means of a sort of combined target- and ligand-based drug design approach. Advantages of this combination strategy, based on a similarity parameter for the identification of weak binding chemical entities, are illustrated in this work with the discovery of a new lead compound for NF-kappaB. Further biochemical analyses based on EMSA were performed and biological effects were tested on the compound exhibiting the best docking score. All experimental analysis were in fairly good agreement with molecular modeling findings.
  
  
  CONCLUSIONS
  The results obtained sustain the concept that the docking performance is predictive of a biochemical activity. In this respect, this paper represents the first example of successfully individuation through molecular docking simulations of a promising lead compound for the inhibition of NF-kappaB-p50 biological activity and modulation of the expression of the NF-kB regulated IL8 gene.
authors.affiliation: BioPharmaNet, ER-GenTech, Department of Biochemistry and Molecular Biology, University of Ferrara, Italy. pcclra@unife.it
authors.forename: Laura
authors.initials: L
authors.lastname: Piccagli
authors.forename: Enrica
authors.initials: E
authors.lastname: Fabbri
authors.forename: Monica
authors.initials: M
authors.lastname: Borgatti
authors.forename: Valentino
authors.initials: V
authors.lastname: Bezzerri
authors.forename: Irene
authors.initials: I
authors.lastname: Mancini
authors.forename: Elena
authors.initials: E
authors.lastname: Nicolis
authors.forename: Maria C
authors.initials: MC
authors.lastname: Dechecchi
authors.forename: Ilaria
authors.initials: I
authors.lastname: Lampronti
authors.forename: Giulio
authors.initials: G
authors.lastname: Cabrini
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambari