2-(2-Phenylethyl)chromone dimers as melanin production inhibitors from agarwood of Gyrinops walla Gaertn

Agarwood is well known to be used and traded as luxurious perfume and cosmetic traditional medicine. Gyrinops walla Gaertn, a newly discovered source of agarwood, has garnered increasing attention. Modern pharmacological studies indicated that 2-(2-phenylethyl)chromones are one of the main chemical constituents in agarwood, known for their diverse biological activities. With the aim to study the cosmetic function of 2-(2-phenylethyl)chromones, phytochemical study on the agarwood from G. walla was carried out, and led to the identification of ten new 2-(2-phenylethyl)chromone dimers. All the structures were elucidated by extensive spectroscopic analysis including 1D and 2D NMR, HR-ESI-MS, as well as ECD calculation. Biological activity showed that all the compounds showed the tyrosinase inhibitory activity with IC₅₀ values ranging from 17.70 ± 1.47–140.30 ± 6.43 μM (kojic acid as the positive control with IC₅₀ value of 24.68 ± 0.30 μM). The kinetic studies presented that compounds 8-10 were competitive inhibitors for tyrosinase, and molecular docking simulations revealed the binding sites and interactions of compounds 3, 4, and 10. Moreover, all the isolated compounds showed a superior inhibitory effect on melanin production in B16 cells compared to kojic acid. Therefore, 2-(2-phenylethyl)chromones could be developed to be melanin production inhibitors used as cosmetic traditional medicine.