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Updated: Jul 16, 2026

Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
Molecular insights into azumamide e histone deacetylases inhibitory activity
Nakia Maulucci1, Maria Giovanna Chini, Simone Di Micco
1Department of Chemistry, University of Salerno, Via Ponte Don Melillo, 84084 Fisciano, Salerno, Italy.
Abstract:
Azumamide E, a cyclotetrapeptide isolated from the sponge Mycale izuensis, is the most powerful carboxylic acid containing natural histone deacetylase (HDAC) inhibitor known to date. In this paper, we describe design and synthesis of two stereochemical variants of the natural product. These compounds have allowed us to clarify the influence of side chain topology on the HDAC-inhibitory activity. The present contribution also reveals the identity of the recognition pattern between azumamides and the histone deacetylase-like protein (HDLP) model receptor and reports the azumamide E unprecedented isoform selectivity on histone deacetylases class subtypes. From the present studies, a plausible model for the interaction of azumamides with the receptor binding pocket is derived, providing a framework for the rational design of new cyclotetrapeptide-based HDAC inhibitors as antitumor agents.
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