Exploration of Novel Mono Hydroxamic Acid Derivatives as Inhibitors for Histone Deacetylase Like Protein (HDLP) by Molecular Dynamics Studies

The acetylation modification process of histone has an essential role in the epigenetic regulation gene expression. This is controlled by balance between deacetylases (HDAC) and acetyltransferases (HAT). HDACs are thought to be vital for cell function. Particularly, higher HDAC expression frequent various cancers, resulting dysregulation several target genes involved proliferation, differentiation, survival. In this study, inhibitory feasibility inhibitors was investigated, including vorinostat (SAHA), N-hydroxy-3-phenylprop-2-enamide (CPD1), N-hydroxy-3-(pyridine-4-yl)prop-2-enamide (CPD2), N-hydroxy-3-(pyridine-2-yl)prop-2-enamide (CPD3), 4-(diphenylamino)-N-(5-(hydroxyamino)-5-oxopentyl)benzamide (CPD4), 2-(6-(((6-fluoronaphthalen-2-yl)methyl)amino)-3-azabicyclo[3.1.0]hex-3-yl)-N-hydroxypirimidine-5-carboxamide (CPD5), N-(3-aminopropyl)-N-hydroxy-2-((naphthalene-1-yloxy)methyl)oct-2-enediamide (CPD6). By examining stability enzyme, positional individual amino acids, binding energies HDLP-inhibitor complexes, assessed. complexes HDLP enzyme with SAHA, CPD4, CPD5, CPD6 had than other studied according results trajectory analysis Ramachandran plot. Based on calculated MM-PBSA free energies, followed order CPD4 > CPD5 SAHA CPD2 CPD3 CPD1. drugability values same trend as previous ones. obtained silico results, were discovered possible lead compounds reference SAHA.