In silico Molecular Interaction Studies of Chiral Heterocyclic Analogs of SAHA as Selective Histone Deacetylase 8 Inhibitors
HDAC8-selective inhibitors not only explore the biological functions of HDAC8 but also
proved to be immensely significant anticancer agents with few side effects. Of the several classifications,
hydroxamic acid-based HDAC inhibitors proved that they produce therapeutic potential against
cutaneous T-cell lymphomas (CTCL). By considering the skeleton of the hydrophobic pocket of
HDAC8 and its catalytic site, about 52 chiral heterocyclic hydroxamic acid derivatives were designed
as inhibitors using structure based drug design approach. Herein, we generated common feature pharmacophore
for mapping the designed ligands. Furthermore, these ligands were subjected to docking
by C DOCKER method and the binding energy was calculated. In addition, toxicity was predicted using ADMET and
TOPKAT simulations. Finally, by combining the results of the above studies, compounds with good binding energy and
less toxicity were considered as the best inhibitors. However, five compounds CMP 9, 25, 26, 33 and 38 successfully satisfied
all the studies among the 52 compounds screened and appeared to be a promising potent inhibitors against HDAC8.
Keywords: HDAC8i, chiral heterocyclic, pharmacophore, C DOCKER, ADMET, TOPKAT.
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