Identification of Potent Caspase-3 Inhibitors for Treatment of Multi- Neurodegenerative Diseases Using Pharmacophore Modeling and Docking Approaches

Author(s): Khurshid Ahmad, Vishal M. Balaramnavar, Mohammad H. Baig, Ashwini K. Srivastava, Saif Khan, Mohammad A. Kamal.

Journal Name: CNS & Neurological Disorders - Drug Targets

Volume 13 , Issue 8 , 2014

Abstract:

Neurodegenerative disorders are due to excessive neuronal apoptosis and the caspase-3 plays a key role in the apoptotic pathway. The caspase-3 inhibition may be a validated therapeutic approach for neurodegenerative disorders and an interesting target for molecular modeling studies using both Ligand and structure based approaches. In view of the above we have generated the Ligand based pharmacophore model using the Discovery studio 2.0 software. In addition to this a structure based approach has been used to validate the developed pharmacophoric features to gain a deeper insight into its molecular recognition process. This validated pharmacophore and the docking model was then implemented as a query for pharmacophore based virtual screening to prioritize the probable hits for the Caspase-3. Two ligands, ZINC12405015 and ZINC12405043 were finally selected on the basis of their fit values and docking scores. This study also reveals the important amino acids viz. His-121, Ser-205, Arg-207 which were found to be playing crucial role in the binding of the selected compounds within the active site of caspase-3.

Keywords: Caspase-3, docking, multi-neurodegenerative disorders, virtual screening.

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Article Details

VOLUME: 13
ISSUE: 8
Year: 2014
Page: [1346 - 1353]
Pages: 8
DOI: 10.2174/1871527313666141023120843
Price: $58

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