Identification of novel leads as potent inhibitors of HDAC3 using ligand-based pharmacophore modeling and MD simulation.

ABSTRACT: In the landscape of epigenetic regulation, histone deacetylase 3 (HDAC3) has emerged as a prominent therapeutic target for the design and development of candidate drugs against various types of cancers and other human disorders. Herein, we have performed ligand-based pharmacophore modeling, virtual screening, molecular docking, and MD simulations to design potent and selective inhibitors against HDAC3. The predicted best pharmacophore model 'Hypo 1' showed excellent correlation (R² = 0.994), lowest RMSD (0.373), lowest total cost value (102.519), and highest cost difference (124.08). Hypo 1 consists of four salient pharmacophore features viz. one hydrogen bond acceptor (HBA), one ring aromatic (RA), and two hydrophobic (HYP). Hypo 1 was validated by Fischer's randomization with

SUBMITTER: Kumbhar N 

PROVIDER: S-EPMC8810932 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature