Next Article in Journal
The Use of a Molybdenum Polyoxometalated Compound to Increase the Amount of Extractives from Wood Wastes
Next Article in Special Issue
A Marine Diterpenoid Modulates the Proteasome Activity in Murine Macrophages Stimulated with LPS
Previous Article in Journal
Adverse Outcome Prediction of Iron Deficiency in Patients with Acute Coronary Syndrome
Open AccessFeature PaperArticle

Flavonoids as Putative Epi-Modulators: Insight into Their Binding Mode with BRD4 Bromodomains Using Molecular Docking and Dynamics

Facultad de Química, Departamento de Farmacia, Universidad Nacional Autónoma de México, Avenida Universidad 3000, Mexico City 04510, Mexico
*
Authors to whom correspondence should be addressed.
Biomolecules 2018, 8(3), 61; https://doi.org/10.3390/biom8030061
Received: 22 June 2018 / Revised: 14 July 2018 / Accepted: 18 July 2018 / Published: 23 July 2018
Flavonoids are widely recognized as natural polydrugs, given their anti-inflammatory, antioxidant, sedative, and antineoplastic activities. Recently, different studies showed that flavonoids have the potential to inhibit bromodomain and extraterminal (BET) bromodomains. Previous reports suggested that flavonoids bind between the Z and A loops of the bromodomain (ZA channel) due to their orientation and interactions with P86, V87, L92, L94, and N140. Herein, a comprehensive characterization of the binding modes of fisetin and the biflavonoid, amentoflavone, is discussed. To this end, both compounds were docked with BET bromodomain 4 (BRD4) using four docking programs. The results were post-processed with protein–ligand interaction fingerprints. To gain further insight into the binding mode of the two natural products, the docking results were further analyzed with molecular dynamics simulations. The results showed that amentoflavone makes numerous contacts in the ZA channel, as previously described for flavonoids and kinase inhibitors. It was also found that amentoflavone can potentially make contacts with non-canonical residues for BET inhibition. Most of these contacts were not observed with fisetin. Based on these results, amentoflavone was experimentally tested for BRD4 inhibition, showing activity in the micromolar range. This work may serve as the basis for scaffold optimization and the further characterization of flavonoids as BET inhibitors. View Full-Text
Keywords: docking; epigenetics; epi-informatics; molecular interactions; molecular dynamics; natural products; flavonoids docking; epigenetics; epi-informatics; molecular interactions; molecular dynamics; natural products; flavonoids
Show Figures

Graphical abstract

MDPI and ACS Style

Prieto-Martínez, F.D.; Medina-Franco, J.L. Flavonoids as Putative Epi-Modulators: Insight into Their Binding Mode with BRD4 Bromodomains Using Molecular Docking and Dynamics. Biomolecules 2018, 8, 61.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop