6533b860fe1ef96bd12c3077
RESEARCH PRODUCT
3D-QSAR pharmacophore modeling and in silico screening of new Bcl-xl inhibitors.
Marco TutoneAntonino LauriaAnna Maria Almericosubject
PharmacologyModels MolecularVirtual screeningQuantitative structure–activity relationshipTertiary amineMolecular modelChemistryIn silicoOrganic ChemistryMolecular Conformationbcl-X ProteinQuantitative Structure-Activity RelationshipGeneral MedicineSettore CHIM/08 - Chimica FarmaceuticaBiochemistryIn vivoDocking (molecular)Drug Discovery3D-QSAR Pharmacophore Modeling In Silico Screening Bcl-xl InhibitorsPharmacophoredescription
Bcl-2 proteins family members play several roles in tumoral proliferation: they inhibit proapoptotic activity during oncogenesis, support tumor cells survival, induce chemoresistance. The discovery of new small inhibitors of Bcl-xl represents a new frontier for cancer treatment. In this study, a 3D-QSAR pharmacophore model was developed, based on 42 biarylacylsulfonamides, and used to understand the structural factors affecting the inhibitory potency of these derivatives. Aromatic, negative charge, and hydrogen bond acceptor effects contribute to the inhibitory activity. The model was then employed as 3D search query to screen ZINC drug-like database in order to select new scaffolds. Finally six hits were identified. Docking study evidenced the capability of these compounds to interact with Bcl-xl receptor, and they were selected for further in vitro and in vivo assay studies.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2010-02-09 | European journal of medicinal chemistry |