title: Histone deacetylase and microtubules as targets for the synthesis of releasable conjugate compounds.
abstract: Design and synthesis of an HDAC inhibitor and its merger with three tubulin binders to create releasable conjugate compounds is described. The biological evaluation includes: (a) in vitro reactivity with glutathione, (b) antiproliferative activity, (c) cell cycle analysis and (d) quantification of protein acetylation. The cellular pharmacology study indicated that the HDAC-inhibitor-drug conjugates retained antimitotic and proapoptotic activity with a reduced potency.
authors.affiliation: Dipartimento di Chimica Organica e Industriale, Università degli Studi di Milano, Via Venezian 21, Italy. Daniele.Passarella@unimi.it
authors.forename: Daniele
authors.initials: D
authors.lastname: Passarella
authors.forename: Daniela
authors.initials: D
authors.lastname: Comi
authors.forename: Andrea
authors.initials: A
authors.lastname: Vanossi
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Paganini
authors.forename: Francesco
authors.initials: F
authors.lastname: Colombo
authors.forename: Luca
authors.initials: L
authors.lastname: Ferrante
authors.forename: Valentina
authors.initials: V
authors.lastname: Zuco
authors.forename: Bruno
authors.initials: B
authors.lastname: Danieli
authors.forename: Franco
authors.initials: F
authors.lastname: Zunino
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D015195:Drug Design; D005978:Glutathione / Q000378:metabolism*; D006367:HeLa Cells; D056464:Histone Deacetylase 2 / Q000037:antagonists & inhibitors*; D006655:Histone Deacetylases / Q000737:chemistry; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D008869:Microtubule-Associated Proteins; D014404:Tubulin; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases; D005978:Glutathione