title: 7,9-Diaryl-1,6,8-trioxaspiro[4.5]dec-3-en-2-ones: readily accessible and highly potent anticancer compounds.
abstract: 7,9-Diaryl-1,6,8-trioxaspiro[4.5]dec-3-en-2-ones are a recently described group of spirocyclic butenolides that can be generated rapidly and as a single diastereomer through a cascade process between γ-hydroxybutenolides and aromatic aldehydes. The following outlines our findings that these spirocycles are potently cytotoxic and have a dramatic structure-function profile that provides excellent insight into the structural features required for this potency.
authors.affiliation: Department of Chemistry, Brooklyn College, The City University of New York, 2900 Bedford Avenue, Brooklyn, NY 11210, United States; Department of Chemistry, The Graduate Center, The City University of New York, 365 Fifth Avenue, New York, NY 10016, United States.
authors.forename: Michael P
authors.initials: MP
authors.lastname: D'Erasmo
authors.affiliation: Department of Medical Oncology, Dayna-Farber Cancer Institute, Boston, MA 02215, United States.
authors.forename: William B
authors.initials: WB
authors.lastname: Smith
authors.affiliation: Department of Chemistry, Brooklyn College, The City University of New York, 2900 Bedford Avenue, Brooklyn, NY 11210, United States.
authors.forename: Alberto
authors.initials: A
authors.lastname: Munoz
authors.affiliation: Department of Biology, Brooklyn College, The City University of New York, 2900 Bedford Avenue, Brooklyn, NY 11210, United States; Department of Biology, The Graduate Center, The City University of New York, 365 Fifth Avenue, New York, NY 10016, United States.
authors.forename: Poornima
authors.initials: P
authors.lastname: Mohandas
authors.affiliation: Department of Biology, Brooklyn College, The City University of New York, 2900 Bedford Avenue, Brooklyn, NY 11210, United States.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Au
authors.affiliation: Department of Medical Oncology, Dayna-Farber Cancer Institute, Boston, MA 02215, United States.
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Marineau
authors.affiliation: Department of Biology, Brooklyn College, The City University of New York, 2900 Bedford Avenue, Brooklyn, NY 11210, United States; Department of Biology, The Graduate Center, The City University of New York, 365 Fifth Avenue, New York, NY 10016, United States.
authors.forename: Luis E N
authors.initials: LE
authors.lastname: Quadri
authors.affiliation: Department of Medical Oncology, Dayna-Farber Cancer Institute, Boston, MA 02215, United States; Department of Medicine, Harvard Medical School, Boston, MA 02215, United States.
authors.forename: James E
authors.initials: JE
authors.lastname: Bradner
authors.affiliation: Department of Chemistry, Brooklyn College, The City University of New York, 2900 Bedford Avenue, Brooklyn, NY 11210, United States; Department of Chemistry, The Graduate Center, The City University of New York, 365 Fifth Avenue, New York, NY 10016, United States. Electronic address: rpmurelli@brooklyn.cuny.edu.
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Murelli
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects / Q000254:growth & development; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D020102:Mycobacterium smegmatis / Q000187:drug effects / Q000254:growth & development; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D013141:Spiro Compounds
keywords: Cancer; Cascade processes; Covalent modifiers; Novel cytotoxic scaffolds; Structure–function studies