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Design of Fluorescent Coumarin-Hydroxamic Acid Derivatives as Inhibitors of HDACs: Synthesis, Anti-proliferative Evaluation and Docking Studies
| Content Provider | MDPI |
|---|---|
| Author | Santiago, García Itzel, Mercado-Sánchez Marco, García-Revilla Nancy, Santos-Martínez Roc, ío García-Becerra Bahena, Luis Alcaraz, Yolanda Robles, Juvencio Ordaz-Rosado, David Vazquez, Miguel |
| Copyright Year | 2020 |
| Description | Coumarin-hydroxamic acid derivatives 7a–k were herein designed with a dual purpose: as antiproliferative agents and fluorescent probes. The compounds were synthesized in moderate yields (30–87%) through a simple methodology, biological evaluation was carried out on prostate (PC3) and breast cancer (BT-474 and MDA-MB-231) cell lines to determine the effects on cell proliferation and gene expression. For compounds 7c, 7e, 7f, 7i and 7j the inhibition of cancer cell proliferation was similar to that found with the reference compound at a comparable concentration (10 μM), in addition, their molecular docking studies performed on histone deacetylases 1, 6 and 8 showed strong binding to the respective active sites. In most cases, antiproliferative activity was accompanied by greater levels of cyclin-dependent kinase inhibitor p21, downregulation of the p53 tumor suppressor gene, and regulation of cyclin D1 gene expression. We conclude that compounds 7c, 7e, 7f, 7i and 7j may be considered as potential anticancer agents, considering their antiproliferative properties, their effect on the regulation of the genes, as well as their capacity to dock to the active sites. The fluorescent properties of compound 7j and 7k suggest that they can provide further insight into the mechanism of action. |
| Starting Page | 5134 |
| e-ISSN | 14203049 |
| DOI | 10.3390/molecules25215134 |
| Journal | Molecules |
| Issue Number | 21 |
| Volume Number | 25 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2020-11-04 |
| Access Restriction | Open |
| Subject Keyword | Molecules Medicinal Chemistry Keywords: Coumarins Hydroxamic Acids Hdac Gene Expression Fluorescent Probe Docking Analysis |
| Content Type | Text |
| Resource Type | Article |
