title: Synthesis and biological activities of a new class of heat shock protein 90 inhibitors, designed by energy-based pharmacophore virtual screening.
abstract: The design through energy-based pharmacophore virtual screening has led to aminocyanopyridine derivatives as efficacious new inhibitors of Hsp90. The synthesized compounds showed a good affinity for the Hsp90 ATP binding site in the competitive binding assay. Moreover, they showed an excellent antiproliferative activity against a large number of human tumor cell lines. Further biological studies on the derivative with the higher EC50 confirmed its specific influence on the cellular pathways involving Hsp90.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche "STEBICEF", Sezione di Chimica Farmaceutica e Biologica, Università di Palermo, Via Archirafi 32, I-90123 Palermo, Italy. antonino.lauria@unipa.it
authors.forename: Antonino
authors.initials: A
authors.lastname: Lauria
authors.forename: Ilenia
authors.initials: I
authors.lastname: Abbate
authors.forename: Carla
authors.initials: C
authors.lastname: Gentile
authors.forename: Francesca
authors.initials: F
authors.lastname: Angileri
authors.forename: Annamaria
authors.initials: A
authors.lastname: Martorana
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Almerico
mesh_terms: D000631:Aminopyridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D013329:Structure-Activity Relationship; D014584:User-Computer Interface
chemical_list: D000631:Aminopyridines; D018841:HSP90 Heat-Shock Proteins