Discriminations of Actives from Inactives HDAC8 Inhibitors: Molecular Modeling Study to Explore Essential Molecular Fingerprints
Posted: 7 Feb 2020
Date Written: February 6, 2020
Objective: Histone deacetylase 8 (HDAC8) is related to various biological pathways and pathophysiological conditions including different cancer progression and epigenetic regulations. The activity of HDAC8 is correlated with a number of cancers such as lung, ovarian, pancreatic, colon and breast cancers as well as leukemia. Because of such contributions of HDAC8 in different pathophysiological states, this specific HDAC8 isoform has readily become a target of effective anticancer drug therapy which is always a challenging task to the chemistry audiences.
Methods: A structurally diverse set comprising large numbers of small molecules were subjected to molecular modeling analysis to discriminate these compounds into HDAC8 inhibitors (active) and non-inhibitors (inactive).
Results: Some pivotal structural and physicochemical descriptors along with molecular fingerprints that regulate HDAC8 activity were identified. The importance of such fingerprints was further validated by the HDAC8 and its inhibitors interactions at the receptor level. These results are found to be in close agreement with our previous works and validate the results of each other.
Conclusions: This work is an initiative to acquire knowledge about the structural and physicochemical parameters important in designing potential HDAC8 inhibitors in future. This comparative learning between the biology and intelligent methods surely accelerate HDAC8 drug discovery process.
Keywords: Cancer, HDAC8 inhibitor, QSAR, classification model, molecular fingerprint, ECFP_6, receptor-ligand interaction
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