title: Identification of biphenyl-based hybrid molecules able to decrease the intracellular level of Bcl-2 protein in Bcl-2 overexpressing leukemia cells.
abstract: With the aim of enhancing the structural complexity and diversity of an existing collection of bi- and terphenyl compounds, we synthesized hybrid molecules comprising of spirocyclic ketones (a complexity-bearing core) and bi/terphenyls (privileged fragments). Compounds 1, 3, 4, and 6 showed well-defined activity on apoptosis and differentiation, making them potential leads for development as new anticancer agents and chemical probes to study signaling networks in neoplastic cells.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University and the Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02138, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Pizzirani
authors.forename: Marinella
authors.initials: M
authors.lastname: Roberti
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: Manlio
authors.initials: M
authors.lastname: Tolomeo
authors.forename: Maurizio
authors.initials: M
authors.lastname: Recanatini
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013730:Terphenyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D007659:Ketones; D019253:Proto-Oncogene Proteins c-bcl-2; D013141:Spiro Compounds; D013730:Terphenyl Compounds