Direct Amidation to Access 3-Amido-1,8-Naphthalimides Including Fluorescent Scriptaid Analogues as HDAC Inhibitors
| Autor: | Nuri Gueven, Rameshwor Acharya, Frederick M. Pfeffer, Kyle N Hearn, Trent D. Ashton, Zikai Feng |
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| Rok vydání: | 2021 |
| Předmět: |
Indoles
1 8-naphthalimide QH301-705.5 medicine.drug_class Buchwald–Hartwig Naphthalenes 010402 general chemistry Hydroxamic Acids Hydroxylamines 01 natural sciences Article Histone Deacetylases chemistry.chemical_compound tubulin deacetylase HDAC Amide medicine Biology (General) Tubulin deacetylation 010405 organic chemistry Chemistry Histone deacetylase inhibitor imaging Acetylation General Medicine HDAC6 Fluorescence Combinatorial chemistry Amides 0104 chemical sciences Naphthalimides Histone Deacetylase Inhibitors scriptaid histone deacetylase Lactam Quinolines fluorescence Histone deacetylase |
| Zdroj: | Cells Volume 10 Issue 6 Cells, Vol 10, Iss 1505, p 1505 (2021) |
| ISSN: | 2073-4409 |
| Popis: | Methodology to access fluorescent 3-amido-1,8-naphthalimides using direct Buchwald–Hartwig amidation is described. The protocol was successfully used to couple a number of substrates (including an alkylamide, an arylamide, a lactam and a carbamate) to 3-bromo-1,8-naphthalimide in good yield. To further exemplify the approach, a set of scriptaid analogues with amide substituents at the 3-position were prepared. The new compounds were more potent than scriptaid at a number of histone deacetylase (HDAC) isoforms including HDAC6. Activity was further confirmed in a whole cell tubulin deacetylation assay where the inhibitors were more active than the established HDAC6 selective inhibitor Tubastatin. The optical properties of these new, highly active, compounds make them amenable to cellular imaging studies and theranostic applications. |
| Databáze: | OpenAIRE |
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