Expanding the Structural Diversity of DNA Methyltransferase Inhibitors
| Autor: | Norberto Sánchez-Cruz, Fernando D. Prieto-Martínez, K. Eurídice Juárez-Mercado, José L. Medina-Franco, Diego Prada-Gracia, Andrea Peña-Castillo |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Methyltransferase natural products Pharmaceutical Science DNA Methyltransferase Inhibitor lcsh:Medicine lcsh:RS1-441 multitarget epigenetic agent focused library environment and public health chemoinformatics Article lcsh:Pharmacy and materia medica 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Panobinostat Drug Discovery Epigenetics enzyme inhibition biology epigenetics Drug discovery Chemistry urogenital system lcsh:R dietary component 030104 developmental biology Histone epi-informatics Biochemistry Docking (molecular) 030220 oncology & carcinogenesis embryonic structures biology.protein DNMT1 Molecular Medicine |
| Zdroj: | Pharmaceuticals Pharmaceuticals, Vol 14, Iss 17, p 17 (2021) Volume 14 Issue 1 |
| ISSN: | 1424-8247 |
| Popis: | Inhibitors of DNA methyltransferases (DNMTs) are attractive compounds for epigenetic drug discovery. They are also chemical tools to understand the biochemistry of epigenetic processes. Herein, we report five distinct inhibitors of DNMT1 characterized in enzymatic inhibition assays that did not show activity with DNMT3B. It was concluded that the dietary component theaflavin is an inhibitor of DNMT1. Two additional novel inhibitors of DNMT1 are the approved drugs glyburide and panobinostat. The DNMT1 enzymatic inhibitory activity of panobinostat, a known pan inhibitor of histone deacetylases, agrees with experimental reports of its ability to reduce DNMT1 activity in liver cancer cell lines. Molecular docking of the active compounds with DNMT1, and re-scoring with the recently developed extended connectivity interaction features approach, led to an excellent agreement between the experimental IC50 values and docking scores. |
| Databáze: | OpenAIRE |
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