Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	A Computational Approach for the Discovery of Novel DNA Methyltransferase Inhibitors
Δημιουργός/Συγγραφέας:	Kritsi, Eftichia Christodoulou, Paris Tsiaka, Thalia [EL] Γεωργιάδης, Παναγιώτης[EN] Georgiadis, Panagiotis [EL] Ζερβού, Μαρία[EN] Zervou, Maria
Ημερομηνία:	2024-04-16
Γλώσσα:	Αγγλικά
ISSN:	1467-3045
DOI:	10.3390/cimb46040213
Άλλο:	38666943
Περίληψη:	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.
Τίτλος πηγής δημοσίευσης:	Current issues in molecular biology
Τόμος/Κεφάλαιο:	46
Τεύχος:	4
Θεματική Κατηγορία:	[EL] Δομική Βιολογία[EN] Structural Biology [EL] Μοριακή Βιολογία[EN] Molecular Biology [EL] Φαρμακευτική χημεία[EN] Pharmaceutical chemistry [EL] Νεοπλάσματα. Όγκοι. Ογκολογία (περ. Καρκίνος, κακινογόνες ουσίες)[EN] Neoplasms. Tumors. Oncology (Incl.cancer, carcinogens) [EL] Χημική Βιολογία[EN] Chemical Biology
Λέξεις-Κλειδιά:	DNA methyltransferases DNMT inhibitors Epigenetics Natural-derived chemo-libraries Pharmacophore modeling Virtual screening
EU Grant:	Reinforcement of Postdoctoral Researchers—2nd Cycle
EU Grant identifier:	2019-050-0503-17828 MIS-5033021
Κάτοχος πνευματικών δικαιωμάτων:	© 2024 by the authors. Licensee MDPI, Basel, Switzerland.
Όροι και προϋποθέσεις δικαιωμάτων:	This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://doi.org/10.3390/cimb46040213
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο