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.

Structure-Based Design and Molecular Dynamics Simulations of Pentapeptide AEYTR as a Potential Acetylcholinesterase Inhibitor

“…Current advances in computational medicinal chemistry can significantly increase the efficiency of drug discovery [6]. Integration of available and accessible computational tools is highly encouraged to avoid pitfalls in computer-aided drug discovery [6][7][8][9][10][11]. One of the suggested integration is the "focused integration", which employs filtering molecules to compile a focused library that contains only compatible and favorable molecules to be screened subsequently [10][11][12].…”

Binary Quantitative Structure-Activity Relationship Analysis in Retrospective Structure-Based Virtual Screening Campaigns Targeting Estrogen Receptor Alpha

“…The distance between the PLIF of the predicted pose and the PLIF of the reference pose calculated using Tanimoto metric results in Tc-IFP [1] or Tc-PLIF [7], which could be used as alternative scoring functions in structure-based virtual screening (SBVS) campaigns [3,4,[12][13][14][15]. Notably, this scoring function is a reference-dependent function, and the selection of the reference determines the predictive quality of the SBVS protocol [3,16].…”

The Cytotoxic Activity on T47D Breast Cancer Cell of Genistein -Standardized Ethanolic Extract of tempeh -A Fermented Product of Soybean ( Glycine Max)

“…has been consumed for centuries and widely known as dietary sources for isoflavones, especially in many Asian countries 1,2 .Soyfoods intake was associated with lower risk of breast and prostate cancer 1,3 and coronary heart disease independent on cholesterol and fracture effects 1 . Moreover, a high soy diet showed memory improvement, which could be associated with activities of histone deacetylases (HDACs) 3,4 . Similar to other phytoestrogens, the isoflavones from soybean have activities in cancer cells resulted from their activity as ligands for estrogen receptors 2,5,6 , a biomarker of breast cancer [7][8][9] .Notably, genistein is the most popular studied isoflavones and has been used as the reference ligand for estrogen receptors, both estrogen receptor a (ERa)and estrogen receptor b (ERb) 10,11 .…”