Coumarins from Casimiroa edulis and their retinoic acid receptor agonist activity

Thirty-nine coumarins were isolated from the leaves and roots of Casimiroa edulis La Llave (Rutaceae). Three of these were identified as new prenylated furocoumarins, named casedulins A-C (1-3). Their structures, including absolute configurations, were determined by 2D-NMR spectral analyses and time-dependent density-functional theory (TDDFT) calculations of specific rotations and ECD spectra. This study provides the first detailed report on the diversity of coumarins in the roots of C. edulis, revealing that while linear furocoumarins are common to both the leaves and roots, simple bicyclic coumarins are specifically located in the roots. In a retinoic acid receptor α (RARα) luciferase reporter assay, 8-geranyloxypsoralen hydrate (18) was found to moderately promote gene transcription, with an EC₅₀ value of 0.27 μM.