title: Chemosensitizing acridones: in vitro calmodulin dependent cAMP phosphodiesterase inhibition, docking, pharmacophore modeling and 3D QSAR studies.
abstract: Calmodulin inhibitors have proved to play a significant role in sensitizing MDR cancer cells by interfering with cellular drug accumulation. The present investigation focuses on the evaluation of in vitro inhibitory efficacy of chloro acridones against calmodulin dependent cAMP phosphodiesterase (PDE1c). Moreover, molecular docking of acridones was performed with PDE1c in order to identify the possible protein ligand interactions and results thus obtained were compared with in vitro data. In addition an efficient pharmacophore model was developed from a set of 38 chemosensitizing acridones effective against doxorubicin resistant (HL-60/DX) cancer cell lines. Pharmacophoric features such as one hydrogen bond acceptor, one hydrophobic region, a positive ion group and three aromatic rings i.e., AHPRRR have been identified. Ligand based 3D-QSAR was also performed by employing partial least square regression analysis.
authors: Medicinal Chemistry Research Division, Vishnu Institute of Pharmaceutical Education and Research, Narsapur, India.
authors: V V S
authors: VV
authors: Rajendra Prasad
authors: G
authors: G
authors: Deepak Reddy
authors: D
authors: D
authors: Appaji
authors: G J
authors: GJ
authors: Peters
authors: Y C
authors: YC
authors: Mayur
mesh_terms: D054831:Acridones / Q000737:chemistry*; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1 / Q000737:chemistry*; D015195:Drug Design; D018922:HL-60 Cells; D006801:Humans; D006860:Hydrogen Bonding; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship
chemical_list: D054831:Acridones; D008024:Ligands; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1