title: Design, synthesis, and discovery of novel non-peptide inhibitor of Caspase-3 using ligand based and structure based virtual screening approach.
abstract: Caspase-3 belonging to a family of cysteine proteases is main executioner of apoptotic cascade pathway. The inhibitors of this protein are useful in the treatment of cardiomyopathy and neurodegenerative diseases. For the discovery of novel Caspase-3 non-peptide inhibitors from Maybridge database, ligand based and structure based virtual screening methods were used. Quantitative 3D pharmacophore models were generated using 25 known inhibitors of Caspase-3 and it was used as initial screen to retrieve the hits from the database. These compounds with high estimated activity were analyzed for drug like properties and docking studies were performed, to study the interaction between new hits and active site. One of the hits (AW01208), with good predictions was selected for synthesis and biological screening. This compound showed an inhibition activity against Caspase-3 in SKNH cell lines.
authors.affiliation: Department of Chemistry, Osmania University College for Women, Koti, Hyderabad, India. ravambio@gmail.com
authors.forename: P Jhansi
authors.initials: PJ
authors.lastname: Lakshmi
authors.forename: B V S Suneel
authors.initials: BV
authors.lastname: Kumar
authors.forename: Ravi Shasi
authors.initials: RS
authors.lastname: Nayana
authors.forename: M Srinivas
authors.initials: MS
authors.lastname: Mohan
authors.forename: Ramababu
authors.initials: R
authors.lastname: Bolligarla
authors.forename: Samar K
authors.initials: SK
authors.lastname: Das
authors.forename: M Uday
authors.initials: MU
authors.lastname: Bhanu
authors.forename: Anand K
authors.initials: AK
authors.lastname: Kondapi
authors.forename: Muttineni
authors.initials: M
authors.lastname: Ravikumar
mesh_terms: D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D003198:Computer Simulation; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D016208:Databases, Factual; D015195:Drug Design; D006801:Humans; D008956:Models, Chemical
chemical_list: D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D053148:Caspase 3