Design, synthesis, and biological evaluation of indenoisoquinoline rexinoids with chemopreventive potential.
Basic Information
ID: ALA2321659
Journal: J Med Chem
Title: Design, synthesis, and biological evaluation of indenoisoquinoline rexinoids with chemopreventive potential.
Authors: Conda-Sheridan M, Park EJ, Beck DE, Reddy PV, Nguyen TX, Hu B, Chen L, White JJ, van Breemen RB, Pezzuto JM, Cushman M.
Abstract: 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.
CiteXplore: 23472886
DOI: 10.1021/jm400026k
Patent ID: ┄