Design, synthesis, and biological evaluation of indenoisoquinoline rexinoids with chemopreventive potential

Martin Conda-Sheridan, Eun Jung Park, Daniel E. Beck, P. V.Narasimha Reddy, Trung X. Nguyen, Bingjie Hu, Lian Chen, Jerry J. White, Richard B. Van Breemen, John M. Pezzuto, Mark Cushman

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Nuclear receptors, such as the retinoid X receptor (RXR), are proteins that regulate a myriad of cellular processes. Molecules that function as RXR agonists are of special interest for the prevention and control of carcinogenesis. The majority of these ligands possess an acidic moiety that is believed to be key for RXR activation. This communication presents the design, synthesis, and biological evaluation of both acidic and nonacidic indenoisoquinolines as new RXR ligands. In addition, a comprehensive structure-activity relationship study is presented that identifies the important features of the indenoisoquinoline rexinoids. The ease of modification of the indenoisoquinoline core and the lack of the necessity of a carboxyl group for activity make them an attractive and unusual family of RXR agonists. This work establishes a structural foundation for the design of new and novel rexinoid cancer chemopreventive agents.

Original languageEnglish (US)
Pages (from-to)2581-2605
Number of pages25
JournalJournal of Medicinal Chemistry
Issue number6
StatePublished - Mar 28 2013
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery


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