144973 - direct amidation to access 3.pdf (1.69 MB)
Direct amidation to access 3-Amido-1,8-naphthalimides including fluorescent scriptaid analogues as HDAC inhibitors
journal contribution
posted on 2023-05-21, 00:10 authored by Hearn, KN, Ashton, TD, Acharya, R, Feng, Z, Nuri GuvenNuri Guven, Pfeffer, FMMethodology 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.
History
Publication title
CellsVolume
10Pagination
1-10ISSN
2073-4409Department/School
School of Pharmacy and PharmacologyPublisher
MDPI AGPlace of publication
SwitzerlandRights statement
Copyright: © 2021 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International (CC BY 4.0) license (https://creativecommons.org/licenses/by/4.0/).Repository Status
- Open