Wagner S, Hofmann A, Siedle B, Terfloth L, Merfort I, Gasteiger J. “Development of a Structural Model for NF-κB Inhibition of Sesquiterpene Lactones Using Self-Organizing Neural Networks.” J. Med. Chem.. 2006;49(7):2241-2252.
| Title | Development of a Structural Model for NF-κB Inhibition of Sesquiterpene Lactones Using Self-Organizing Neural Networks |
| Publication Type | Journal Article |
| Year of Publication | 2006 |
| Authors | Wagner S, Hofmann A, Siedle B, Terfloth L, Merfort I, Gasteiger J |
| Journal | J. Med. Chem. |
| Volume | 49 |
| Issue | 7 |
| Pagination | 2241 – 2252 |
| Date Published | 04/2006 |
| ISSN | 0022-2623 |
| Abstract | A variety of sesquiterpene lactones (SLs) possess considerable anti-inflammatory activity. Several studies have shown that they exert this effect in part by inhibiting the activation of the transcription factor NF-κB. In the present study we elaborated on the investigation of a data set of 103 structurally diverse SLs for which we had previously developed several different QSAR equations dependent on the skeletal type. Use of 3D structure descriptors resulted in a single model for the entire data set. In particular, local radial distribution functions (L-RDF) were used that centered on the methylene−carbonyl substructure believed to be the site of attack of cysteine-38 of the p65/NF-κB subunit. The model was developed by using a counterpropagation neural network (CPGNN), attesting to the power of this method for establishing structure−activity-relationships. The investigations shed more light onto the influence of the chemical structure on NF-κB inhibitory activity. |
| DOI | 10.1021/jm051125n |
| Short Title | J. Med. Chem. |