Tyrosinase is a key enzyme in melanin biosynthesis, and is also involved in the enzymatic browning of plant-derived foods. Tyrosinase inhibitors are very important in medicine, cosmetics and agriculture. In order to develop more active and safer tyrosinase inhibitors, an efficient approach is to modify natural product scaffolds. In this work, two series of novel tyrosinase inhibitors were designed and synthesized by the esterification of cinnamic acid derivatives with paeonol or thymol. Their inhibitory effects on mushroom tyrosinase were evaluated. Most of these compounds (IC: 2.0 to 163.8 μM) are found to be better inhibitors than their parent compounds (IC: 121.4 to 5925.0 μM). Among them, ()-2-acetyl-5-methoxyphenyl-3-(4-hydroxyphenyl)acrylate (), ()-2-acetyl-5-methoxyphenyl-3-(4-methoxyphenyl)acrylate () and ()-2-isopropyl-5-methylphenyl-3-(4-hydroxyphenyl)acrylate () showed strong inhibitory activities; the IC values were 2.0 μM, 8.3 μM and 10.6 μM, respectively, compared to the positive control, kojic acid (IC: 32.2 μM). Analysis of the inhibition mechanism of , and demonstrated that their inhibitory effects on tyrosinase are reversible. The inhibition kinetics, analyzed by Lineweaver-Burk plots, revealed that acts as a non-competitive inhibitor while and are mixed-type inhibitors. Furthermore, docking experiments were carried out to study the interactions between and mushroom tyrosinase.

BackgroundFusidic acid (FA) (WU-FA-00) is the only commercially available antimicrobial from the fusidane family that has a narrow spectrum of activity against Gram-positive bacteria.MethodsHerein, the hydrogenation derivative (WU-FA-01) of FA was prepared and both compounds were examined against a panel of six bacterial strains. In addition, their anti-inflammatory properties were evaluated using a 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema model.ResultsThe results of the antimicrobial assay revealed that both WU-FA-00 and WU-FA-01 displayed a high level of antimicrobial activity against Gram-positive strains. Moreover, killing kinetic studies were performed and the results were in accordance with the minimum inhibitory concentration and minimum bactericidal concentration results. We also demonstrated that the topical application of WU-FA-00 and WU-FA-01 effectively decreased TPA-induced ear edema in a dose-dependent manner. This inhibitory effect was associated with the inhibition of TPA-induced upregulation of proinflammatory cytokines IL-1β, TNF-α, and COX-2. WU-FA-01 significantly suppressed the expression levels of p65, IκB-α, and p-IκB-α in the TPA-induced mouse ear model.ConclusionOverall, our results showed that WU-FA-00 and WU-FA-01 not only had effective antimicrobial activities in vitro, especially to the Gram-positive bacteria, but also possessed strong anti-inflammatory effects in vivo. These results provide a scientific basis for developing FA derivatives as antimicrobial and anti-inflammatory agents.

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Two triterpenoids from Acanthopanax trifoliatus, an edible medicinal plant from Southeast Asia, attenuated lipopolysaccharides-induced inflammation in murine macrophage RAW246.7 cells and tetradecanoylphorbolacetate-induced mouse ear edema.