Discovery and Mechanism of Natural Products as Modulators of Histone Acetylation

Lilibeth      A. Salvador; Hendrik      Luesch

Abstract

Small molecules that modulate histone acetylation by targeting key enzymes mediating this posttranslational modification – histone acetyltransferases and histone deacetylases – are validated chemotherapeutic agents for the treatment of cancer. This area of research has seen a rapid increase in interest in the past decade, with the structurally diverse natural products-derived compounds at its forefront. These secondary metabolites from various biological sources target this epigenetic modification through distinct mechanisms of enzyme regulation by utilizing a diverse array of pharmacophores. We review the discovery of these compounds and discuss their modes of inhibition together with their downstream biological effects.

Keywords: Histone acetylation, histone deacetylases, histone acetyltransferases, natural products, secondary metabolites, Natural Products, chemotherapeutic agents, epigenetic modification, enzyme regulation, DNA