A Computational Approach for the Discovery of Novel DNA Methyltransferase Inhibitors.
Curr Issues Mol Biol
; 46(4): 3394-3407, 2024 Apr 16.
Article
en En
| MEDLINE
| ID: mdl-38666943
ABSTRACT
Nowadays, the explosion of knowledge in the field of epigenetics has revealed new pathways toward the treatment of multifactorial diseases, rendering the key players of the epigenetic machinery the focus of today's pharmaceutical landscape. Among epigenetic enzymes, DNA methyltransferases (DNMTs) are first studied as inhibition targets for cancer treatment. The increasing clinical interest in DNMTs has led to advanced experimental and computational strategies in the search for novel DNMT inhibitors. Considering the importance of epigenetic targets as a novel and promising pharmaceutical trend, the present study attempted to discover novel inhibitors of natural origin against DNMTs using a combination of structure and ligand-based computational approaches. Particularly, a pharmacophore-based virtual screening was performed, followed by molecular docking and molecular dynamics simulations in order to establish an accurate and robust selection methodology. Our screening protocol prioritized five natural-derived compounds, derivatives of coumarins, flavones, chalcones, benzoic acids, and phenazine, bearing completely diverse chemical scaffolds from FDA-approved "Epi-drugs". Their total DNMT inhibitory activity was evaluated, revealing promising results for the derived hits with an inhibitory activity ranging within 30-45% at 100 µM of the tested compounds.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Curr Issues Mol Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2024
Tipo del documento:
Article
País de afiliación:
Grecia