Background:
Huntington's disease is characterized by three side effects, including motor
disturbances, psychiatric elements, and intellectual weakness. The onset for HD has nonlinear converse
associations with the number of repeat sequences of the polyglutamine mutations, so that younger patients
have a tendency for longer repeats length. This HD variation is because of the development of a
polyglutamine (CAG) repeats in the exon 1 of the Huntingtin protein.
Methods:
In the present study, a few derivatives utilized as a part of the treatment of HD, are used to
create the pharmacophore model and based on the features of the pharmacophore model; an attempt is
made to design the de-novo drug for the HD protein. HD protein structure was built and docked with
the novel ligand, based on shared feature pharmacophore model, through a ligand-based pharmacophore
modeling approach.
Results:
The novel ligand contains 1 HBAs, 2 HBDs, and 2 aromatic rings. It fulfills all the properties of certain
drug-likeness rules, non-toxic in nature. In the docked complex, the common interactive amino acids
identified are SER 1035, ALA 1062, MET 1068, LEU 1031, and THR 1036, which confirmed the validity
and stability of a ligand molecule to be used as a drug in the treatment of Huntington’s disease.
Conclusion:
A novel ligand can be used in clinical trials as a drug molecule against the mutations of
HD gene and in laboratory procedures for efficacy analysis.
Mechanistic Insights into the Binding of Class IIa HDAC Inhibitors toward Spinocerebellar Ataxia Type-2: A 3D-QSAR and Pharmacophore Modeling Approach
