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Dual RXR Agonists and RAR Antagonists Based on the Stilbene Retinoid Scaffold
Claudio Martínez1, Michele Lieb2, Susana Alvarez1
1Departamento de Química Orgánica, Facultade de Química, CINBIO, Universidade de Vigo, and Instituto de Investigación Biomédica de Vigo (IBIV) , 36310 Vigo, Spain.
Abstract:
Arotinoids containing a C5,C8-diphenylnaphthalene-2-yl ring linked to a (C3-halogenated) benzoic acid via an ethenyl connector (but not the corresponding naphthamides), which are prepared by Horner-Wadsworth-Emmons reaction of naphthaldehydes and benzylphosphonates, display the rather unusual property of being RXR agonists (15-fold induction of the RXR reporter cell line was achieved at 3- to 10-fold lower concentration than 9-cis-retinoic acid) and RAR antagonists as shown by transient transactivation studies. The binding of such bulky ligands suggests that the RXR ligand-binding domain is endowed with some degree of structural elasticity.
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