title: Azetidinone-retinoid hybrids: synthesis and differentiative effects.
abstract: As a part of a systematic investigation on the synthesis and biological activities of new β-lactam compounds, we examined β-lactam candidates 1, 2E and 2Z and their ability to induce cell proliferation or differentiation. Azetidinone 1 was chosen for its activity (previously evaluated) as selective HDAC8 inhibitor, whereas β-lactams 2E and 2Z were designed to have a hybrid retinoid-azetidinone structure, de novo synthesized and fully characterized. Biological activities were determined in cellular assays on neuroblastoma cells SH-SY5Y. Azetidinone 1, 2E and 2Z led to a moderate effect in decreasing SH-SY5Y cell proliferation and β-lactams 2E and 2Z induced an early stage differentiation. The present results uncovered a new role of specifically designed β-lactam compounds in epigenetic regulation.
authors.affiliation: Department of Chemistry "G. Ciamician", University of Bologna, Via Selmi 2, 40126 Bologna, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Pori
authors.forename: Paola
authors.initials: P
authors.lastname: Galletti
authors.forename: Roberto
authors.initials: R
authors.lastname: Soldati
authors.forename: Laura
authors.initials: L
authors.lastname: Calzà
authors.forename: Chiara
authors.initials: C
authors.lastname: Mangano
authors.forename: Daria
authors.initials: D
authors.lastname: Giacomini
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001384:Azetidines / Q000737:chemistry / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D012176:Retinoids / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C116379:2-azetidinone; D000970:Antineoplastic Agents; D001384:Azetidines; D012176:Retinoids
keywords: Cell differentiation; Epigenetic regulation; HDAC inhibitors; Retinoids; Synthesis; β-Lactams