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Direct amidation to access 3-amido-1,8-naphthalimides including fluorescent scriptaid analogues as HDAC inhibitors

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journal contribution
posted on 2021-06-01, 00:00 authored by Kyle Hearn, Trent Ashton, Rameshwor Acharya, Zikai Feng, Nuri Gueven, Fred PfefferFred Pfeffer
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.

History

Journal

Cells

Volume

10

Issue

6

Article number

1505

Pagination

1 - 10

Publisher

MDPI

Location

Basel, Switzerland

ISSN

2073-4409

eISSN

2073-4409

Language

English

Publication classification

C Journal article; C1 Refereed article in a scholarly journal