Pharmacophore Based 3D-QSAR Modeling and Molecular Docking of Leucettines as Potent Dyrk1A Inhibitors
Sandip B. Bharate,
The elevated level of dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A) is associated
with the pathology of neurodegenerative diseases and has been implicated in some neurobiological alterations of Down
syndrome, such as mental retardation. In the present article, a pharmacophore based 3D-QSAR model was developed for a
series of leucettines possessing Dyrk1A inhibitory activity. The crucial molecular features observed in the developed
pharmacophore model that account for binding affinity of ligands with the enzyme, include three H-bond acceptors (A),
one positive ionic site (P) and one hydrophobic aromatic ring (R). Excellent statistical results of QSAR model such as
good correlation coefficient (r > 0.9), higher F value (F > 20), excellent predictive power (Q2 > 0.6) and higher enrichment
of known actives during virtual screening application strongly suggest that the developed model will be highly useful in
designing new inhibitors and for predicting activity of new inhibitors.
Keywords: Anti-Alzheimers, Dyrk1A, Leucettines, Pharmacophore model, 3D-QSAR, Partial least square analysis.
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