Marine terpenoids with antimelanogenic activity from the brown alga <i>Dictyopteris polypodioides</i> in B16 melanoma cells

The brown alga Dictyopteris polypodioides produces a variety of sesquiterpene derivatives. However, its potential as an antimelanogenic agent remains unclear. In this study, we investigated the ability of D. polypodioides extract and its constituent compounds to inhibit melanin biosynthesis. Methanolic extracts of D. polypodioides significantly suppressed melanin accumulation in B16 melanoma 4A5 cells. We identified four sesquiterpene hydroquinone derivatives, zonarol (1), yahazunol (2), isozonarol (3), and chromazonarol (6), as active constituents. Structure-activity relationship analyses, including those of semisynthetic analogs, indicated that the hydroquinone moiety is crucial for the antimelanogenesis activity. Chromazonarol (6), which lacks a hydroquinone group, inhibits tyrosinase (monophenolase) in an uncompetitive manner, with 50% inhibitory concentration of 6.2 µm. Quantitative analysis revealed that these sesquiterpene derivatives accounted for approximately 5.6% of the dried algal biomass. D. polypodioides is a promising natural source of bioactive compounds with potential applications in preventing melanogenesis and food browning.