title: Alkyl piperidine and piperazine hydroxamic acids as HDAC inhibitors.
abstract: We report here the strategy used in our research group to find a new class of histone deacetylase (HDAC) inhibitors. A series of N-substituted 4-alkylpiperazine and 4-alkylpiperidine hydroxamic acids, corresponding to the basic structure of HDAC inhibitors (zinc binding moiety-linker-capping group) has been designed, prepared, and tested for HDAC inhibition. Linker length and aromatic capping group connection were systematically varied to find the optimal geometric parameters. A new series of submicromolar inhibitors was thus identified, which showed antiproliferative activity on HCT-116 colon carcinoma cells.
authors.affiliation: Menarini Ricerche Pomezia, via Tito Speri 10, 00040 Pomezia, Rome, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Rossi
authors.forename: Marina
authors.initials: M
authors.lastname: Porcelloni
authors.forename: Piero
authors.initials: P
authors.lastname: D'Andrea
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Fincham
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ettorre
authors.forename: Sandro
authors.initials: S
authors.lastname: Mauro
authors.forename: Antonella
authors.initials: A
authors.lastname: Squarcia
authors.forename: Mario
authors.initials: M
authors.lastname: Bigioni
authors.forename: Massimo
authors.initials: M
authors.lastname: Parlani
authors.forename: Federica
authors.initials: F
authors.lastname: Nardelli
authors.forename: Monica
authors.initials: M
authors.lastname: Binaschi
authors.forename: Carlo A
authors.initials: CA
authors.lastname: Maggi
authors.forename: Daniela
authors.initials: D
authors.lastname: Fattori
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006655:Histone Deacetylases / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D010879:Piperazines; D000077489:Piperazine; D006655:Histone Deacetylases