title: Identification of potent caspase-3 inhibitors for treatment of multi- neurodegenerative diseases using pharmacophore modeling and docking approaches.
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.
authors.forename: Khurshid
authors.initials: K
authors.lastname: Ahmad
authors.forename: Vishal M
authors.initials: VM
authors.lastname: Balaramnavar
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Baig
authors.forename: Ashwini K
authors.initials: AK
authors.lastname: Srivastava
authors.forename: Saif
authors.initials: S
authors.lastname: Khan
authors.affiliation: Department of Biosciences, Integral University, Lucknow, India. mohdhassanbaig@gmail.com.
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Kamal
mesh_terms: D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors / Q000737:chemistry* / Q000627:therapeutic use*; D015195:Drug Design; D006801:Humans; D062105:Molecular Docking Simulation; D019636:Neurodegenerative Diseases / Q000188:drug therapy*; D015203:Reproducibility of Results; D014584:User-Computer Interface
chemical_list: D061945:Caspase Inhibitors; D053148:Caspase 3