Phenolic compounds from Ficus hispida L.f. as tyrosinase and melanin inhibitors: Biological evaluation, molecular docking, and molecular dynamics

Eleven known phenolic compounds 1 – 11 were isolated from the MeOH extract of the fruits of Ficus hispida L.f. (Moraceae), all of which have been investigated inhibitory activities of melanin and tyrosinase in vitro . Compounds 1, 2 , and 5 – 8 exhibited potent melanin inhibitory activities against B16F10 melanoma cells, especially 5,7-dihydroxy-4 ′ -methoxy-3 ′ -(3-methyl-2-hydroxybuten-3-yl)isoflavone ( 2 ) showed superior inhibitory effect with no or weak toxicities even at the concentration of 10 μM. Moreover, the results of western blot analysis and tyrosinase inhibitory activity assay revealed that compound 2 could suppress melanogenesis by inhibiting the expression levels of microphthalmia-associated transcription factor (MITF), tyrosinase-related protein 1 (TRP-1), TRP-2, and tyrosinase in α -melanocyte-stimulating hormone ( α -MSH) stimulated B16F10 melanoma cells. Then, we performed molecular docking and molecular dynamics (MD) simulation studies to explore the binding mode and dynamic properties between compound 2 and mushroom tyrosinase. Molecular docking analysis showed that compound 2 had a strong binding affinity (−4.533 kcal/mol) to mushroom tyrosinase by the interaction of π-cation, π-π stacking, and hydrogen bonding. And the MD simulation study for 10 ns clearly demonstrated the dynamic stability of ligand-protein complex. Taken these results together, compound 2 may serve as a promising candidate for the design and development of potential tyrosinase and melanin inhibitor. l Eleven known phenolic compounds 1 – 11 were isolated from the MeOH extract of the fruits of ficus hispida L.f. (Moraceae). l Compound 2 showed superior inhibitory effect against B16F10 melanoma cells with no or weak toxicities at low concentrations. l The molecular docking and molecular dynamics studies have been performed, indicating that compound 2 had a strong binding affinity (−4.533 kcal/mol) to mushroom tyrosinase.