tretinoin and 2-naphthoic-acid

In search for retinoic acid receptor (RAR) selective ligands, a series of 6-substituted 2-naphthoic acid retinoids were synthesized and evaluated in vitro in a transactivation assay and a competition binding assay for all RARs. These derivatives, in general, showed RAR beta,gamma selectivity. Among these naphthoic acids, oxime derivative 12 was identified as a potent RAR gamma-selective retinoid, while olefinic derivative 11 was found to be comparable to retinoic acid and slightly RAR beta,gamma selective. For the bioassays, a general correlation was observed between the binding affinity of the ligand to the receptors and the potency of the compounds in the transactivation assay. The structure-activity relationship of these naphthoic acids will be discussed.

Topics: Binding, Competitive; Drug Design; Genes, Reporter; HeLa Cells; Humans; Ligands; Molecular Structure; Naphthalenes; Receptors, Retinoic Acid; Recombinant Fusion Proteins; Retinoic Acid Receptor gamma; Retinoids; Structure-Activity Relationship; Substrate Specificity; Transcriptional Activation; Tretinoin