6533b834fe1ef96bd129e018

RESEARCH PRODUCT

Synthesis and biological activities of a new class of heat shock protein 90 inhibitors, designed by energy-based pharmacophore virtual screening

Anna Maria AlmericoIlenia AbbateFrancesca AngileriAnnamaria MartoranaCarla GentileAntonino Lauria

subject

AminopyridinesInhibitory Concentration 50Structure-Activity RelationshipUser-Computer InterfaceHeat shock proteinCell Line TumorSettore BIO/10 - BiochimicaDrug DiscoveryHumansHSP90 Heat-Shock ProteinsBinding siteVirtual screeningheat shock protein 90 inhibitors energy-based pharmacophore virtual screening cell cycle antiproliferative activitybiologyChemistryHsp90Combinatorial chemistrySettore CHIM/08 - Chimica FarmaceuticaHuman tumorMolecular Docking SimulationCell cultureDrug DesignEnergy basedbiology.proteinMolecular MedicinePharmacophoreDrug Screening Assays Antitumor

description

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.

yearjournalcountryeditionlanguage
2013-04-05
10.1021/jm4002023http://hdl.handle.net/10447/73051