title: 4,5,6,7-Tetrahydro-isoxazolo-[4,5-c]-pyridines as a new class of cytotoxic Hsp90 inhibitors.
abstract: Hsp90 is considered an interesting therapeutic target for anticancer drug development. Here we describe a new class of 4,5,6,7-tetrahydro-isoxazolo-[4,5-c]-pyridine compounds. A small library of derivatives has been synthesized and investigated. Some reported compounds show interesting properties combining both notable binding to Hsp90 and potent cell growth inhibitory activity. N-5 substitution with a 2,4 resorcinol carboxamide appears crucial for activity. Moreover, a derivative bearing a hydroxamic acid residue bound to C-3 amide portion was found to inhibit both Hsp90 and HDAC6.
authors.affiliation: Dipartimento di Scienze Chimiche e Farmaceutiche, Università degli Studi di Ferrara, I-44121 Ferrara, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Baruchello
authors.affiliation: Dipartimento di Scienze Chimiche e Farmaceutiche, Università degli Studi di Ferrara, I-44121 Ferrara, Italy. Electronic address: smd@unife.it.
authors.forename: Daniele
authors.initials: D
authors.lastname: Simoni
authors.affiliation: Dipartimento di Scienze Chimiche e Farmaceutiche, Università degli Studi di Ferrara, I-44121 Ferrara, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Marchetti
authors.affiliation: Dipartimento di Scienze Chimiche e Farmaceutiche, Università degli Studi di Ferrara, I-44121 Ferrara, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Rondanin
authors.affiliation: Dipartimento di Scienze Chimiche e Farmaceutiche, Università degli Studi di Ferrara, I-44121 Ferrara, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Mangiola
authors.affiliation: Dipartimento di Scienze Chimiche e Farmaceutiche, Università degli Studi di Ferrara, I-44121 Ferrara, Italy.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Costantini
authors.affiliation: Dipartimento di Scienze per la Promozione della Salute e Materno Infantile, Sezione di Farmacologia, Università di Palermo, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Meli
authors.affiliation: R&D Sigma-Tau Industrie Farmaceutiche Riunite S.p.A., I-00040 Pomezia, Roma, Italy. Electronic address: giuseppe.giannini@sigma-tau.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giannini
authors.affiliation: R&D Sigma-Tau Industrie Farmaceutiche Riunite S.p.A., I-00040 Pomezia, Roma, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Vesci
authors.affiliation: R&D Sigma-Tau Industrie Farmaceutiche Riunite S.p.A., I-00040 Pomezia, Roma, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Carollo
authors.affiliation: R&D Sigma-Tau Industrie Farmaceutiche Riunite S.p.A., I-00040 Pomezia, Roma, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Brunetti
authors.affiliation: R&D Sigma-Tau Industrie Farmaceutiche Riunite S.p.A., I-00040 Pomezia, Roma, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Battistuzzi
authors.affiliation: Centro Interdipartimentale di Ricerca in Oncologia Clinica e Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Malattie Infettive, Università di Palermo, Palermo, Italy.
authors.forename: Manlio
authors.initials: M
authors.lastname: Tolomeo
authors.affiliation: R&D Sigma-Tau Industrie Farmaceutiche Riunite S.p.A., I-00040 Pomezia, Roma, Italy.
authors.forename: Walter
authors.initials: W
authors.lastname: Cabri
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D005434:Flow Cytometry; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D020014:K562 Cells; D009682:Magnetic Resonance Spectroscopy; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D018841:HSP90 Heat-Shock Proteins; D011725:Pyridines
keywords: 4,5,6,7-Tetrahydro-isoxazolo-[4,5-c]-pyridines; Anti-cancer drugs; Heat shock protein 90