Molecular Docking, Synthesis, and Tyrosinase Inhibition Activity of Acetophenone Amide: Potential Inhibitor of Melanogenesis

Tyrosinase and its related proteins are responsible for pigmentation disorders, and inhibiting tyrosinase is an established strategy to treat hyperpigmentation. The carbonyl scaffolds can be effective inhibitors of tyrosinase activity, and the fact that both benzoic and cinnamic acids are safe natural substances with such a scaffolded structure, it was speculated that hydroxyl-substituted benzoic and cinnamic acid derivatives may exhibit potent tyrosinase inhibitory activity. These moieties were incorporated into new chemotypes that displayed in vitro inhibitory effect against mushroom tyrosinase with a view to explore antimelanogenic ingredients. The most active compound, 2-((3-acetylphenyl)amino)-2-oxoethyl(E)-3-(2,4-dihydroxyphenyl)acrylate (5c), inhibited mushroom tyrosinase with an IC50 of 0.0020 ± 0.0002 μ M , while 2-((3-acetylphenyl)amino)-2-oxoethyl 2,4-dihydroxybenzoate (3c) had an IC50 of 27.35 ± 3.6 μ M in comparison to the positive control arbutin and kojic acid with a tyrosinase inhibitory activity of IC50 of 191.17 ± 5.5 μ M and IC50 of 16.69 ± 2.8 μ M , respectively. Analysis of enzyme kinetics revealed that 5c is a competitive and reversible inhibitor with dissociation constant (Ki) value 0.0072 μM. In silico docking studies with mushroom tyrosinase (PDB ID 2Y9X) predicted possible binding modes in the enzymatic pocket for these compounds. The orthohydroxyl of the cinnamic acid moiety of 5c is predicted to form hydrogen bond with the active site side chain carbonyl of Asn 260 (2.16 Å) closer to the catalytic site Cu ions. The acetyl carbonyl is picking up another hydrogen bond with Asn 81 (1.90 Å). The inhibitor 5c passed the panassay interference (PAINS) alerts. This study presents the potential of hydroxyl-substituted benzoic and cinnamic acids and could be beneficial for various cosmetic formulations.

Camellia japonica Essential Oil Inhibits α-MSH-Induced Melanin Production and Tyrosinase Activity in B16F10 Melanoma Cells

Essential oils are aromatic oils extracted from the leaves, stems, peels, petals, and roots of aromatic plants grown in nature or grown in organic methods and have various medical effects as natural substances. The essential oil extracted from Camellia japonica seeds exhibits various functional properties; however, its tyrosinase inhibitory activity has not been investigated extensively. This study is performed to investigate the chemical composition and tyrosinase inhibitory activity of Camellia japonica seed essential oil (CJS-EO). Hexamethylcyclotrisiloxane (42.36%) and octamethylcyclotetrasiloxane (23.28%) are the two primary components of CJS-EO, as identified via gas chromatography-mass spectrometry. The inhibitory activities of CJS-EO and positive control arbutin are further evaluated against mushroom tyrosinase. The results show that CJS-EO and arbutin inhibit tyrosinase activity. Moreover, CJS-EO significantly inhibits melanogenesis in the α-melanocyte-stimulating hormone-treated group, and a significant amount of melanin is suppressed. To ascertain the cause of the CJS-EO tyrosinase inhibitory effect and melanin reduction effect, genetic and protein analyses are performed. Based on our results, we tentatively conclude that CJS-EO can inhibit melanocytes from harmful factors such as tyrosinase-related protein. These results demonstrate that CJS-EO possesses potent antityrosinase activity and may be a good skin-whitening agent.

Synthesis, Molecular Docking and Tyrosinase Inhibitory Activity of the Decorated Methoxy Sulfonamide Chalcones: in vitro Inhibitory Effects and the Possible Binding Mode

In this study, a series of sulfonamide chalcones derivatives was synthesized and its chemical structures were confirmed by spectral characteristics. The synthesized compounds were evaluated for their tyrosinase inhibitory activities along with molecular docking study. The tyrosinase inhibitory results indicated that compounds 5b, 5c, 5f, 5g and 5h displayed the significant tyrosinase inhibitory activity and comparable to the standard drug (kojic acid). Compound 5c exhibits the most potent tyrosinase inhibition among the synthesized compounds with IC50 = 0.43±0.07 mM, L-DOPA as the substrate, and better than that of the standard kojic acid (IC50 = 0.60±0.20 mM). Molecular docking studies showed that the binding mode of some compounds is in the tyrosinase binding pocket surrounding the copper in the active site. The correlation between the docking results with IC50 values showed that the binding mode prediction of the test compounds would also be convincing. This comprehensive study allows for a possible mechanism for the antityrosinase activity of the sulfonamide chalcones. These sulfonamide chalcones bind to copper atoms of tyrosinase which responsible for the catalytic activity of tyrosinase. These compounds may be used as a lead for rational drug designing for the multi-functional tyrosinase inhibitor.

Analyses of the Compositions, Antioxidant Capacities, and Tyrosinase-Inhibitory Activities of Extracts from Two New Varieties of Chrysanthemum morifolium Ramat Using Four Solvents

Chrysanthemum morifolium Ramat is traditionally used as both medicine and food in China. In this study, extracts of C. morifolium Ramat Hang Ju No. 1 (No. 1) and No. 2 (No. 2) were produced using four different solvents: 95% ethanol, ethyl acetate, n-hexane and distilled water. In total, eight types of extracts were analyzed for extraction yields and total flavonoids, polyphenols, glycans, reducing sugars, and chlorogenic acids. The antioxidant capacities and tyrosinase-inhibitory activities of these extracts were also determined. Among them, the ethanolic extract of No. 1 (No. 1A) had the highest levels of total flavonoids (16.71 mg rutin equivalent/g dry weight (DW)), polyphenols (7.07 mg gallic acid equivalent/g DW), and chlorogenic acids (6595.46 μg/g DW) and the water extract of No. 1 (No. 1D) had the highest levels of total glycans (9.24 mg/g DW), and reducing sugars (23.32 μg/g DW). In terms of antioxidant capacity, No. 1A (1.0 mg/mL) demonstrated the best 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity (96.2 ± 0.4%), ferrous ion chelating ability (55.44 ± 0.03%), and reducing power (0.988 ± 0.003). No. 1D (1.0 mg/mL) showed the highest tyrosinase inhibitory activity (39.34 ± 0.03%). From these results, high levels of total flavonoids and polyphenols correlate with antioxidant capacity. Moreover, high levels of total chlorogenic acid in No. 1A and No. 1D correlate with high levels of tyrosinase inhibitory activity. Therefore, No. 1A has the potential to be used in daily health drinks, foods and skin whitening products. These results can be applied to similar flower plant extracts.

Extraction, Purification of Tyrosinase and Tyrosinase Inhibitory Activity of Four Medicinal Plants from Nanded District (MS), India

Tyrosinase has an important role in melanin formation, is responsible for the production of colour pigments of skin, hair, and eye. In the presents study, tyrosinase was isolated from Mushrooms, isolation of enzyme was done by acetone precipitation procedure and precipitation of enzyme was done with ammonium sulphate precipitation method. Plants selected for extraction were Azadirachta indica (Neem), Manikara zapota (Chiku), Annona squamosa (Sitaphal), and Hibiscus Rosa-sinesis (China rose). For phytochemical screening Alkaloids-Mayer’s Test, Flavonoids (Shinoda Test, Alkaline Reagent Test), sugar (Benedict’s reagent Test), Glycosides (Borntrager's Test), Phenolic compounds Test (Ferric chloride Test, Gelatin Test, Lead Acetate Test). Mushroom tyrosinase inhibitory assay was determined by the spectroscopic method. The study shows the tyrosinase inhibitory activity of selected medicinal plants.