A Structure–Activity Relationship Study of the Antimalarial and Antileishmanial Activities of Nonpeptide Macrocyclic Histone Deacetylase Inhibitors

Abstract

Histone deacetylase inhibitors (HDACi) cause a diverse range of responses in biological systems. The depth of the antiparasitic capabilities of macrocyclic HDACi was determined against malarial and leishmanial pathogens. Antiparasitic activities of macrocyclic HDACi derived from macrolide skeletons are dependent on the length (n) of the spacer group that separates their zinc-binding and surface-recognition moieties. Antimalarial activities peak when n=6, whereas antileishmanial activities are optimum when n=8–9. This observation could facilitate the identification of other HDACi that are more selective for either parasite. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.