Browsing by Author "Alnemsi, Fatma"

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    Master Thesis
    Docking Study of Resveratrol Like Molecules on Histone Deacetylase
    (Kadir Has Üniversitesi, 2016) Alnemsi, Fatma; Yelekçi, Kemal; Yelekçi, Kemal
    The modulation of histone acetylation plays a pivotal role in the regulation of gene expression by governing the state of lysine residues located on the amino – terminal tails of histone proteins. A dynamic balance of histone acetylation /deacetylation is maintained by histone acetyl transferases(HAT) and histone deacetylases(HDACs) . Due to their fundamental role in gene expression HDAC family have been associated with basic cellular events and disease states such as cell growth differentiation and cancer information. in particular distinct class i and ii are overexpressed in some cancer disease. HDAC inhibitors structurally can be grouped into hydroxamates cyclic peptides aliphatic acids benzamine’s. HDAC inhibitors (HDACi) and histone acetyl transferase activators increase histone acetylation. HDAC8 is a class i HDAC implicated as a therapeutic target for a various disease including disorder cell growth. The structure of this enzyme reaveled unique features as its conformational flexibility. The architecture of the catalytic site and the channel rim of HDAC8 adapt to accommodate various ligands according to their size shape and chemical properties. Ýn this study the native TSA ligand of HDAC8 (code 1T64) re docked to observe the inhibition constant (Ki) with different parameter such as rotatable bonds and X Y Z coordinates. From this approach starting de nova design from resveratrol compound that is suggested to play a role in the preventation of some disease such as inhibition of tumour initiation. The resveratrol scaffold was used to create 100 hundred analogues by substituting chemical groups to observe the changes in the binding energy and inhibition constant by molecular docking using Autodock4.2. These 100 analogues were evaluated in terms of the inhibition constant (Ki) and 20 of them selected due to their lowest inhibition constant (Ki) and binding energy. The fact that HDAC8 is a promising target for cancer therapy these molecules can be potential anticancer agents if additional laboratory assays are carried out to ascertain their inhibitory effects.