Development of Stilbenoid and Chalconoid Analogues as Potent Tyrosinase Modulators and Antioxidant Agents.

A number of stilbenoid and chalconoid derivatives were prepared by straightforward methods, and their ability to modulate tyrosinase activity and to scavenge free radicals were evaluated in vitro. The cell-free in vitro evaluation revealed two diarylpropanes, 24 and 25, as potent tyrosinase inhibitors, whereas diarylpropenoic acids seemed to enhance the enzymatic activity. An in silico evaluation of the binding affinity of the selected compounds with the crystal structure of tyrosinase was also conducted in order to obtain better insight into the mechanism. Representative synthetic compounds with inhibitory and activating properties were further evaluated in melanoma cell lines B16F1 and B16F10 for their ability to moderate tyrosinase activity and affect melanin production. Dihydrostilbene analogues I and II, exhibited a stronger anti-melanogenic effect than kojic acid through the inhibition of cellular tyrosinase activity and melanin formation, while diarylpropanoic acid 44 proved to be a potent melanogenic factor, inducing cellular tyrosinase activity and melanin formation. Moreover, the antioxidant evaluation disclosed two analogues (29 and 11) with significant free-radical-scavenging activity (12.4 and 20.3 µM), which were 10- and 6-fold more potent than ascorbic acid (122.1 µΜ), respectively.

Anti-Melanogenic Properties of Greek Plants. A Novel Depigmenting Agent from Morus alba Wood.

In therapeutic interventions associated with melanin hyperpigmentation, tyrosinase is regarded as a target enzyme as it catalyzes the rate-limiting steps in mammalian melanogenesis. Since many known agents have been proven to be toxic, there has been increasing impetus to identify alternative tyrosinase inhibitors, especially from natural sources. In this study, we investigated 900 extracts from Greek plants for potential tyrosinase inhibitive properties. Among the five most potent extracts, the methanol extract of Morus alba wood (MAM) demonstrated a significant reduction in intracellular tyrosinase and melanin content in B16F10 melanoma cells. Bioassay-guided isolation led to the acquisition of twelve compounds: oxyresveratrol (1), kuwanon C (2), mulberroside A (3), resorcinol (4), dihydrooxyresveratol (5), trans-dihydromorin (6), 2,4,3'-trihydroxydihydrostilbene (7), kuwanon H (8), 2,4-dihydroxybenzaldehyde (9), morusin (10), moracin M (11) and kuwanon G (12). Among these, 2,4,3'-trihydroxydihydrostilbene (7) is isolated for the first time from Morus alba and constitutes a novel potent tyrosinase inhibitor (IC50 0.8 ± 0.15). We report here for the first time dihydrooxyresveratrol (5) as a potent natural tyrosinase inhibitor (IC50 0.3 ± 0.05). Computational docking analysis indicated the binding modes of six tyrosinase inhibitors with the aminoacids of the active centre of tyrosinase. Finally, we found both MAM extract and compounds 1, 6 and 7 to significantly suppress in vivo melanogenesis during zebrafish embryogenesis.

Correlation of total polyphenolic content with antioxidant and antibacterial activity of 24 extracts from Greek domestic Lamiaceae species.

Lamiaceae family species are considered important because of their use in folk medicine, culinary and flavouring throughout the world. Their interesting bioactivities are attributed mainly to essential oils, polyphenols and terpenes. However, there are only few studies about polyphenolic extracts from Lamiaceae plants. Thus, 24 polyphenolic extracts from three Lamiaceae genera, Salvia, Mentha and Sideritis, collected in Greece were examined for antioxidant and antibacterial activity in correlation with their polyphenolic content. The results showed that the tested polyphenolic extracts had strong free radical scavenging activity against DPPH· and ABTS(+) radicals and protected from hydroxyl and peroxyl radical-induced DNA damage. Moreover, five extracts inhibited Staphylococcus aureus growth. Furthermore, the results showed that the total polyphenolic content is not correlated with the above activities, although this relation was different within each plant genus. This is the first study regarding the antioxidant and antibacterial activity of Salvia pomifera ssp. calycina, S. pomifera ssp. pomifera, Mentha microphylla and Sideritis raeseri ssp. attica species, and one of the few concerning protection from DNA damage and antibacterial activity of polyphenolic extracts from the rest of the tested species.