title: Antiproliferative agents that interfere with the cell cycle at the G1-->S transition: further development and characterization of a small library of stilbene-derived compounds.
abstract: In this continuation of our research on derivatives containing the stilbene privileged structure or that are derived from it, we report the results of further studies carried out on the previously initiated collection of compounds. We used a parallel synthetic approach to rapidly obtain small sets of compounds and started the annotation of the library in progress by calculating some physicochemical properties to be eventually correlated with biological activities. A pharmacophore for the antiproliferative activity was also built to summarize the features of the library. We evaluated the antiproliferative and pro-apoptotic activities of all compounds as well as the cell-cycle effects of some representative compounds. After in-depth investigations, 3'-phenyl-[1,1';4',1'']terphenyl-4,3'',5''-triol showed the most interesting biological profile, as it interferes with cell-cycle progression at the G(1)-->S transition, acting on retinoblastoma phosphorylation and inducing cell differentiation.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Pizzirani
authors.forename: Marinella
authors.initials: M
authors.lastname: Roberti
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavalli
authors.forename: Stefania
authors.initials: S
authors.lastname: Grimaudo
authors.forename: Antonietta
authors.initials: A
authors.lastname: Di Cristina
authors.forename: Rosaria Maria
authors.initials: RM
authors.lastname: Pipitone
authors.forename: Nicola
authors.initials: N
authors.lastname: Gebbia
authors.forename: Manlio
authors.initials: M
authors.lastname: Tolomeo
authors.forename: Maurizio
authors.initials: M
authors.lastname: Recanatini
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects* / Q000502:physiology; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D010766:Phosphorylation; D012175:Retinoblastoma / Q000737:chemistry / Q000378:metabolism; D016196:S Phase / Q000187:drug effects* / Q000502:physiology; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000494:pharmacology*; D013267:Stilbenes / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D054852:Small Molecule Libraries; D013267:Stilbenes