Structure-based virtual screening campaigns on curcuminoids as potent ligands for histone deacetylase-2

Abstract

Curcumin was reported to reverse the decrease in histone deacetylase-2 (HDAC2) protein expression in inflammatory diseases of the lung, including chronic obstructive pulmonary disease (COPD), severe asthma, and asthma in smokers. This indicates that curcumin is a potent ligand for HDAC2. The construction and retrospective validation of a structure-based virtual screening (SBVS) protocol to identify potent ligands for HDAC2 are presented in this article. The validated protocol was subsequently employed to screen curcumin and other curcuminoids found in Curcuma longa, i.e.demethoxycurcumin and bis-demethoxycurcumin, and to examine their interactions to HDAC2 in the atomic level. The results show that curcumin, demethoxycurcumin and bis-demethoxycurcumin are potent HDAC2 ligands. The insights from their interactions to HDAC2 resulted from the molecular docking simulations presented in this article could be employed further in the design and discovery potent HDAC2 ligands.