HSQC-based SMART accelerated discovery of a new picane triterpene with tyrosinase inhibitory activity from Palhinhaea cernua

Chemical investigation on Palhinhaea cernua by HSQC-based small molecule accurate recognition technology (SMART) resulted in the rapid discovery of four triterpenes, including a new triterpene ( 1 ) with a rare picane-type carbon framework. The chemical structure of 1 was elucidated by analysis of spectral data. Moreover, the absolute configuration of 1 was established by TDDFT-ECD and QM-NMR calculations. Compounds 1 and 2 displayed significant tyrosinase inhibitory effects (IC 50 = 123.6 and 184.6 μM), which were similar to the positive control ascorbic acid (IC 50 = 128.1 μM). Docking study disclosed the multiple stabilizing interactions between 1 and oxy-tyrosinase. Moreover, molecular dynamics (MD) simulations and binding free energy analyses further validated the stable accommodation of compound 1 within the protein binding pocket.