7,9-Diaryl-1,6,8-trioxaspiro[4.5]dec-3-en-2-ones: readily accessible and highly potent anticancer compounds

Michael P D'Erasmo; William B Smith; Alberto Munoz; Poornima Mohandas; Andrew S Au; Jason J Marineau; Luis E N Quadri; James E Bradner; Ryan P Murelli

doi:10.1016/j.bmcl.2014.05.102

7,9-Diaryl-1,6,8-trioxaspiro[4.5]dec-3-en-2-ones: readily accessible and highly potent anticancer compounds

Bioorg Med Chem Lett. 2014 Aug 15;24(16):4035-8. doi: 10.1016/j.bmcl.2014.05.102. Epub 2014 Jun 12.

Authors

Michael P D'Erasmo¹, William B Smith², Alberto Munoz³, Poornima Mohandas⁴, Andrew S Au⁵, Jason J Marineau², Luis E N Quadri⁴, James E Bradner⁶, Ryan P Murelli⁷

Affiliations

¹ 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.
² Department of Medical Oncology, Dayna-Farber Cancer Institute, Boston, MA 02215, United States.
³ Department of Chemistry, Brooklyn College, The City University of New York, 2900 Bedford Avenue, Brooklyn, NY 11210, United States.
⁴ 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.
⁵ Department of Biology, Brooklyn College, The City University of New York, 2900 Bedford Avenue, Brooklyn, NY 11210, United States.
⁶ Department of Medical Oncology, Dayna-Farber Cancer Institute, Boston, MA 02215, United States; Department of Medicine, Harvard Medical School, Boston, MA 02215, United States.
⁷ 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: [email protected].

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.

Keywords: Cancer; Cascade processes; Covalent modifiers; Novel cytotoxic scaffolds; Structure–function studies.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Bacillus subtilis / drug effects
Bacillus subtilis / growth & development
Cell Line, Tumor
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Escherichia coli / drug effects
Escherichia coli / growth & development
Humans
Microbial Sensitivity Tests
Molecular Conformation
Mycobacterium smegmatis / drug effects
Mycobacterium smegmatis / growth & development
Spiro Compounds / chemical synthesis
Spiro Compounds / chemistry
Spiro Compounds / pharmacology*
Structure-Activity Relationship

Substances

Anti-Bacterial Agents
Antineoplastic Agents
Spiro Compounds

Abstract

Publication types

MeSH terms

Substances

Grants and funding