LC-MS- and NMR-Guided Isolation of Monoterpene Dimers from Cultivated Thymus vulgaris Varico 3 Hybrid and Their Antityrosinase Activity

Targeted isolation based on a combination of NMR and HPLC-PDA-MS of a dichloromethane extract of Thymus vulgaris Varico 3 aerial parts afforded one new p-cymene dimer, 6,3',4'-trihydroxy-5,5'-diisopropyl-2,2'-dimethylbiphenyl (1), together with two known p-cymene derivatives (2 and 3), as well as five known compounds, namely, thymol (4), oleanolic acid (5), ursolic acid (6), cirsimaritin (7), and xanthomicrol (8). The structural elucidation of all compounds was performed by spectroscopic analyses, including 1D and 2D NMR, and HRESIMS experiments. The biphenyls were assayed for their inhibitory activity on tyrosinase. Compounds 2 and 3 showed negligible activity on tyrosinase, while compound 1 effectively inhibited the enzyme with 35% (+/- 0.3) inhibitory activity, higher than the inhibition of the reference compound kojic acid (18.6 +/- 0.02).