Inverse Virtual Screening allows the discovery of the biological activity of natural compounds

Gianluigi Lauro; Milena Masullo; Sonia Piacente; Raffaele Riccio; Giuseppe Bifulco

doi:10.1016/j.bmc.2012.03.072

Inverse Virtual Screening allows the discovery of the biological activity of natural compounds

Bioorg Med Chem. 2012 Jun 1;20(11):3596-602. doi: 10.1016/j.bmc.2012.03.072. Epub 2012 Apr 6.

Authors

Gianluigi Lauro¹, Milena Masullo, Sonia Piacente, Raffaele Riccio, Giuseppe Bifulco

Affiliation

¹ Dipartimento di Scienze Farmaceutiche e Biomediche, Università di Salerno, Via Ponte Don Melillo, 84084 Fisciano (SA), Italy.

PMID: 22537682
DOI: 10.1016/j.bmc.2012.03.072

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
Drug Evaluation, Preclinical / methods*
Drug Screening Assays, Antitumor
Flavonoids / chemistry
Flavonoids / pharmacology
Hydrophobic and Hydrophilic Interactions
Inhibitory Concentration 50
Models, Molecular*
Phenols / chemistry
Phenols / pharmacology
Propiophenones / chemistry
Propiophenones / pharmacology
Protein Kinase C / antagonists & inhibitors
Protein Kinase C / metabolism
Protein Kinase C beta
Protein Kinase C-alpha / antagonists & inhibitors
Protein Kinase C-alpha / metabolism
Protein Kinase Inhibitors / chemistry*
Protein Kinase Inhibitors / metabolism
Protein Kinase Inhibitors / pharmacology
Protein Serine-Threonine Kinases / antagonists & inhibitors
Protein Serine-Threonine Kinases / metabolism
Pyruvate Dehydrogenase Acetyl-Transferring Kinase
Software
User-Computer Interface
Xanthones / chemistry
Xanthones / pharmacology

Substances

Flavonoids
Phenols
Propiophenones
Protein Kinase Inhibitors
Pyruvate Dehydrogenase Acetyl-Transferring Kinase
Xanthones
isoxanthohumol
Protein Serine-Threonine Kinases
Protein Kinase C
Protein Kinase C beta
Protein Kinase C-alpha
xanthohumol