title: Psoralen derivatives as inhibitors of NF-κB/DNA interaction: synthesis, molecular modeling, 3D-QSAR, and biological evaluation.
abstract: Some new psoralen derivatives were synthesized and evaluated as inhibitors of NF-κB/DNA interaction, with the aim to investigate the structural determinants required to inhibit this interaction. Starting from molecular docking studies, several possible protein binding sites were proposed and several three-dimensional quantitative structure-activity relationship (3D-QSAR) models were built using the docked poses of 29 (the most active psoralen in the series) as templates for alignment of the inhibitors. The selected best model was validated through the prediction of the activity of 17 novel compounds. All the experimental data agreed with the computational experiments, supporting the reliability of the computational approach. The hypothesis about the interaction with NF-κB was also supported by surface plasmon resonance based assays using compound 29. All the collected data allowed the identification of compound 29 as a potential candidate for the development of pharmaceutical strategies against the inflammatory phenotype of cystic fibrosis.
authors: Dipartimento di Scienze del Farmaco, Università degli Studi di Padova, Via Marzolo 5, 35131 Padova, Italy.
authors: Giovanni
authors: G
authors: Marzaro
authors: Adriano
authors: A
authors: Guiotto
authors: Monica
authors: M
authors: Borgatti
authors: Alessia
authors: A
authors: Finotti
authors: Roberto
authors: R
authors: Gambari
authors: Giulia
authors: G
authors: Breveglieri
authors: Adriana
authors: A
authors: Chilin
mesh_terms: D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001665:Binding Sites; D003550:Cystic Fibrosis / Q000188:drug therapy; D004247:DNA / Q000037:antagonists & inhibitors / Q000378:metabolism; D011564:Furocoumarins / Q000138:chemical synthesis / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D056004:Molecular Dynamics Simulation; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D020349:Surface Plasmon Resonance
chemical_list: D000893:Anti-Inflammatory Agents; D011564:Furocoumarins; D016328:NF-kappa B; D004247:DNA