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 (IC₅₀: 2.0 to 163.8 μM) are found to be better inhibitors than their parent compounds (IC₅₀: 121.4 to 5925.0 μM). Among them, (E)-2-acetyl-5-methoxyphenyl-3-(4-hydroxyphenyl)acrylate (5a), (E)-2-acetyl-5-methoxyphenyl-3-(4-methoxyphenyl)acrylate (5g) and (E)-2-isopropyl-5-methylphenyl-3-(4-hydroxyphenyl)acrylate (6a) showed strong inhibitory activities; the IC₅₀ values were 2.0 μM, 8.3 μM and 10.6 μM, respectively, compared to the positive control, kojic acid (IC₅₀: 32.2 μM). Analysis of the inhibition mechanism of 5a, 5g and 6a demonstrated that their inhibitory effects on tyrosinase are reversible. The inhibition kinetics, analyzed by Lineweaver–Burk plots, revealed that 5a acts as a non-competitive inhibitor while 5g and 6a are mixed-type inhibitors. Furthermore, docking experiments were carried out to study the interactions between 6a and mushroom tyrosinase.

Background: Fusidic 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. Methods: Herein, 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. Results: The 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. Conclusion: Overall, 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.

Mosquitoes are one of the most important disease vectors from a medical viewpoint in that they transmit several diseases such as malaria, filariasis, yellow and Dengue fever. Mosquito vector control and personal protection from mosquito bites are currently the most efficient ways to prevent these diseases. Several synthetic repellents such as DEET, ethyl butylacetylaminopropionate (IR3535) and 1-(1-methylpropoxycarbonyl)-2-(2-hydroxyethyl)piperidine) (Picaridin), have been widely used to prevent humans from receiving mosquito bites. However, the use of synthetic repellents has raised several environment and health concerns. Therefore, essential oils (EOs) as natural alternatives receive our attention. In order to discover highly effective mosquito repellents from natural sources, the repellent activity of 60 commercial EOs against Ae. albopictus was screened in this study. Eight EOs including cinnamon, marjoram, lemongrass, bay, chamomile, jasmine, peppermint2, and thyme, showed a suitable repellent rate (>40%) at the tested dose of 10 μg/cm². Then, their main constituents were analyzed by GC-MS, and the active constituents were identified. The most active compounds including cinnamaldehyde, citral and terpinen-4-ol, exhibited an 82%, 65% and 60% repellent rate, respectively. Moreover, the nanoemulsions of the three active compounds were prepared and characterized. In the arm-in-cage assay, the protection times of the nanoemulsions of cinnamaldehyde and citral were significantly extended compared with their normal solutions. This study provides several lead compounds to develop new mosquito repellents, and it suggests that nanoemulsification is an effective method for improving the duration of the activity of natural repellents.