title: Inverse Virtual Screening allows the discovery of the biological activity of natural compounds.
abstract: A small library of phenolic natural compounds belonging to different chemical classes was screened on a panel of targets involved in the genesis and progression of cancer. The re-investigation of their potential activity was achieved through the Inverse Virtual Screening approach. The normalization of the predicted binding energies permitted the selection of promising compounds on definite targets, avoiding the selection of false positive results. In vitro biological tests revealed the inhibitory activity of xanthohumol and isoxanthohumol on PDK1 and PKC protein kinases. This study validates the robustness of the Inverse Virtual Screening in silico approach as a useful tool for the identification of the specific biological activity of a given set of compounds.
authors.affiliation: Dipartimento di Scienze Farmaceutiche e Biomediche, Università di Salerno, Via Ponte Don Melillo, 84084 Fisciano (SA), Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Lauro
authors.forename: Milena
authors.initials: M
authors.lastname: Masullo
authors.forename: Sonia
authors.initials: S
authors.lastname: Piacente
authors.forename: Raffaele
authors.initials: R
authors.lastname: Riccio
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bifulco
mesh_terms: D001665:Binding Sites; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004354:Drug Screening Assays, Antitumor; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology; D011427:Propiophenones / Q000737:chemistry / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D012984:Software; D014584:User-Computer Interface; D044004:Xanthones / Q000737:chemistry / Q000494:pharmacology
chemical_list: D005419:Flavonoids; D010636:Phenols; D011427:Propiophenones; D047428:Protein Kinase Inhibitors; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D044004:Xanthones; C512910:isoxanthohumol; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; C104536:xanthohumol