Mushroom Tyrosinase Inhibition Research Articles

Exploration of Compounds with 2-Phenylbenzo[d]oxazole Scaffold as Potential Skin-Lightening Agents through Inhibition of Melanin Biosynthesis and Tyrosinase Activity.

Inspired by the potent tyrosinase inhibitory activity of phenolic compounds with a 2-phenylbenzo[d]thiazole scaffold, we explored phenolic compounds 1-15 with 2-phenylbenzo[d]oxazole, which is isosterically related to 2-phenylbenzo[d]thiazole, as novel tyrosinase inhibitors. Among these, compounds 3, 8, and 13, featuring a resorcinol structure, exhibited significantly stronger mushroom tyrosinase inhibition than kojic acid, with compound 3 showing a nanomolar IC50 value of 0.51 μM. These results suggest that resorcinol plays an important role in tyrosinase inhibition. Kinetic studies using Lineweaver-Burk plots demonstrated the inhibition mechanisms of compounds 3, 8, and 13, while docking simulation results indicated that the resorcinol structure contributed to tyrosinase binding through hydrophobic and hydrogen bonding interactions. Additionally, these compounds effectively inhibited tyrosinase activity and melanin production in B16F10 cells and inhibited B16F10 tyrosinase activity in situ in a concentration-dependent manner. As these compounds showed no cytotoxicity to epidermal cells, melanocytes, or keratinocytes, they are appropriate for skin applications. Compounds 8 and 13 demonstrated substantially higher depigmentation effects on zebrafish larvae than kojic acid, even at 800- and 400-times lower concentrations than kojic acid, respectively. These findings suggest that 2-phenylbenzo[d]oxazole is a promising candidate for tyrosinase inhibition.

Elucidating bis-pyrimidines as new and efficient mushroom tyrosinase inhibitors: synthesis, SAR, kinetics and computational studies.

In this study, a series of novel bis-pyrimidine derivatives (1P-8P) were designed, synthesized, characterized, and investigated for their in vitro inhibitory activity against mushroom tyrosinase, an enzyme critical in melanin biosynthesis and implicated in various hyperpigmentation disorders. To the best of our knowledge, the bispyrimidine scaffold has been evaluated for the first time for its tyrosinase inhibitory activity. Their inhibitory activities were assessed, revealing inhibition with IC50 values in the micromolar range. Additionally, this series of compounds were found to inhibit tyrosinase activity in a mixed-type manner, with IC50 values ranging from 12.36 ± 1.24 to 86.67 ± 3.08 μM. To further elucidate the binding interactions, molecular docking simulations were performed, identifying key residues in the active site responsible for binding affinity. Furthermore, molecular dynamics (MD) simulations were conducted to assess the dynamic behavior, stability, and binding affinity of the most potent inhibitor, compound 6P. Quantitative Structure-Activity Relationship (QSAR) models were developed to correlate the structural features of the bis-pyrimidines with their inhibitory activity, providing insights into the structure-activity relationships (SAR) that govern their potency. The experimental and theoretical findings demonstrated excellent agreement. These findings pave the way for the development of novel bis-pyrimidine-based therapeutic agents for treating hyperpigmentation and related conditions.

Prenylated flavonoids from Sophora flavescens inhibit mushroom tyrosinase activity and modulate melanogenesis in murine melanoma cells and zebrafish.

Background: Sophora flavescens, a traditional Chinese medicine for treating conditions associated with abnormal skin pigmentation, contains flavonoids with inhibitory effects on tyrosinase. However, their mechanisms of action and their modulatory effects on melanogenesis remain unclear. Methods: Herein, a group of prenylated flavonoids was identified from S. flavescens extracts and their inhibitory activities on mushroom tyrosinase were evaluated. The anti-melanogenesis effects of these prenylated flavonoids were investigated in cellular (with murine melanoma cells) and animal (with zebrafish) models. Results: Prenylated flavonoids including isoanhydroicaritin (IAI), kurarinone (KR), and sophoraflavanone G (SG) were the major active constituents in S. flavescens extracts with anti-tyrosinase activity (IC50 = 0.7, 7.1, and 6.7μM, respectively). Enzyme kinetic assays showed that IAI, KR, and SG had a mixed type of tyrosinase inhibition, supported by data from computational docking. Notably, KR at concentrations of 5 and 10μM enhanced intracellular tyrosinase activity and stimulated melanin production in B16F10 cells, whereas SG and IAI did not exhibit significant activity. Further studies with the zebrafish model showed that IAI (80 and 160μM) inhibited melanin biosynthesis by about 30.0% while KR (20μM) stimulated melanogenesis by 36.9%. Furthermore, a zebrafish depigmentation model supported the anti-melanogenesis effect of IAI (80 and 160μM) by 33.0% and 34.4%, respectively. Conclusion: In summary, IAI was identified as a tyrosinase inhibitor with an anti-melanogenic effect and KR was an enhancer for melanin production in B16F10 cells and zebrafish. Findings from the current study suggest that IAI and KR from S. flavescens may exert contrasting effects in the modulation of melanin production, providing important insights into the development of S. flavescens as a cosmeceutical or medicinal ingredient.

Phenylalanine Butyramide: A Butyrate Derivative as a Novel Inhibitor of Tyrosinase.

Metabolites resulting from the bacterial fermentation of dietary fibers, such as short-chain fatty acids, especially butyrate, play important roles in maintaining gut health and regulating various biological effects in the skin. However, butyrate is underutilized due to its unpleasant odor. To circumvent this organoleptic unfavorable property, phenylalanine butyramide (PBA), a butyrate precursor, has been synthesized and is currently available on the market. We evaluated the inhibition of mushroom tyrosinase by butyrate and PBA through in vitro assays, finding IC50 values of 34.7 mM and 120.3 mM, respectively. Docking calculations using a homology model of human tyrosinase identified a putative binding mode of PBA into the catalytic site. The anti-aging and anti-spot efficacy of topical PBA was evaluated in a randomized, double-blind, parallel-arm, placebo-controlled clinical trial involving 43 women affected by photo-damage. The results of this study showed that PBA significantly improved skin conditions compared to the placebo and was well tolerated. Specifically, PBA demonstrated strong skin depigmenting activity on both UV and brown spots (UV: -12.7% and -9.9%, Bs: -20.8% and -17.7% after 15 and 30 days, respectively, p < 0.001). Moreover, PBA brightened and lightened the skin (ITA°: +12% and 13% after 15 and 30 days, respectively, p < 0.001). Finally, PBA significantly improved skin elasticity (Ua/Uf: +12.4% and +32.3% after 15 and 30 days, respectively, p < 0.001) and firmness (Uf: -3.2% and -14.9% after 15 and 30 days, respectively, p < 0.01).

Investigation of the Efficacy of Benzylidene-3-methyl-2-thioxothiazolidin-4-one Analogs with Antioxidant Activities on the Inhibition of Mushroom and Mammal Tyrosinases.

Based on the fact that substances with a β-phenyl-α,β-unsaturated carbonyl (PUSC) motif confer strong tyrosinase inhibitory activity, benzylidene-3-methyl-2-thioxothiazolidin-4-one (BMTTZD) analogs 1-8 were prepared as potential tyrosinase inhibitors. Four analogs (1-3 and 5) inhibited mushroom tyrosinase strongly. Especially, analog 3 showed an inhibitory effect that was 220 and 22 times more powerful than kojic acid in the presence of l-tyrosine and l-dopa, respectively. A kinetic study utilizing mushroom tyrosinase showed that analogs 1 and 3 competitively inhibited tyrosinase, whereas analogs 2 and 5 inhibited tyrosinase in a mixed manner. A docking simulation study indicated that analogs 2 and 5 could bind to both the tyrosinase active and allosteric sites with high binding affinities. In cell-based experiments using B16F10 cells, analogs 1, 3, and 5 effectively inhibited melanin production; their anti-melanogenic effects were attributed to their ability to inhibit intracellular tyrosinase activity. Moreover, analogs 1, 3, and 5 inhibited in situ B16F10 cellular tyrosinase activity. In three antioxidant experiments, analogs 2 and 3 exhibited strong antioxidant efficacy, similar to that of the positive controls. These results suggest that the BMTTZD analogs are promising tyrosinase inhibitors for the treatment of hyperpigmentation-related disorders.

Patchouli Alcohol: A Potent Tyrosinase Inhibitor Derived from Patchouli Essential Oil with Potential in the Development of a Skin-Lightening Agent

The inhibitory effects of Pogostemon cablin essential oil (patchouli essential oil, PEO) and its primary bioactive compound, patchouli alcohol (PA), on tyrosinase and melanin were investigated in vitro and ex vivo. Treatment with PEO and PA significantly, as well as dose-dependently, reduced forskolin (FRK)-induced melanin biosynthesis, cellular tyrosinase activity, and tyrosinase (TYR) protein expression. However, the transcriptional levels of TYR and tyrosinase-related proteins (TRP-1 and TRP-2) remained unaffected. These results suggest that PEO and PA may directly interrupt tyrosinase enzyme activity, leading to a reduction in melanin biosynthesis. Further experiments supported this notion, revealing that both PEO and PA significantly and dose-dependently inhibited mushroom tyrosinase activity in both the monophenolase and diphenolase phases. Additionally, an in silico molecular docking analysis was performed, utilizing a homology model of human tyrosinase. In conclusion, these findings strongly suggest that patchouli essential oil and its primary bioactive component, patchouli alcohol, hold promise as potential treatments for hyperpigmentary skin conditions and in the development of cosmetic products designed to lighten the skin.

Pulp or Peel? Comparative Analysis of the Phytochemical Content and Selected Cosmetic-Related Properties of Annona cherimola L., Diospyros kaki Thumb., Cydonia oblonga Mill. and Fortunella margarita Swingle Pulp and Peel Extracts.

Fruit peels might be a valuable source of active ingredients for cosmetics, leading to more sustainable usage of plant by-products. The aim of the study was to evaluate the phytochemical content and selected biological properties of hydroglycolic extracts from peels and pulps of Annona cherimola, Diospyros kaki, Cydonia oblonga, and Fortunella margarita as potential cosmetic ingredients. Peel and pulp extracts were compared for their antiradical activity (using DPPH and ABTS radical scavenging assays), skin-lightening potential (tyrosinase inhibitory assay), sun protection factor (SPF), and cytotoxicity toward human fibroblast, keratinocyte, and melanoma cell lines. The total content of polyphenols and/or flavonoids was significantly higher in peel than in pulp extracts, and the composition of particular active compounds was also markedly different. The HPLC-MS fingerprinting revealed the presence of catechin, epicatechin and rutoside in the peel of D. kaki, whereas kaempferol glucoside and procyanidin A were present only in the pulp. In A. cherimola, catechin, epicatechin and rutoside were identified only in the peel of the fruit, whereas procyanidins were traced only in the pulp extracts. Quercetin and luteolinidin were found to be characteristic compounds of F. margarita peel extract. Naringenin and hesperidin were found only in the pulp of F. margarita. The most significant compositional variety between the peel and pulp extracts was observed for C. oblonga: Peel extracts contained a higher number of active components (e.g., vicenin-2, kaempferol rutinoside, or kaempferol galactoside) than pulp extract. The radical scavenging potential of peel extracts was higher than of the pulp extracts. D. kaki and F. margarita peel and pulp extracts inhibited mushroom and murine tyrosinases at comparable levels. The C. oblonga pulp extract was a more potent mushroom tyrosinase inhibitor than the peel extract. Peel extract of A. cherimola inhibited mushroom tyrosinase but activated the murine enzyme. F. margarita pulp and peel extracts showed the highest in vitro SPF. A. cherimola, D. kaki, and F. margarita extracts were not cytotoxic for fibroblasts and keratinocytes up to a concentration of 2% (v/v) and the peel extracts were cytotoxic for A375 melanoma cells. To summarize, peel extracts from all analyzed fruit showed comparable or better cosmetic-related properties than pulp extracts and might be considered multifunctional active ingredients of skin lightening, anti-aging, and protective cosmetics.

Green fabrication of silver nanoparticles and it’s in vitro anti-bacterial, anti-biofilm, free radical scavenging and mushroom tyrosinase efficacy evaluation

This paper reports a fast, reliable, and efficient protocol for the synthesis of silver nanoparticles using the medicinal plant Paeonia Japonica (PJ) root extract and the in-vitro biological activities of the synthesized AgNPs. The results of XRD and TEM analysis showed that the particles are in 28 nm size with spherical morphology. The PJ–AgNPs portrayed excellent anti-bacterial activity against the gram (+ve) and (−ve) microorganism studied in dose dependent manner. It exhibits very good anti-biofilm activity against the pathogenic S. Aureus with respect to the dose used (89 % inhibition at 100 µg/mL dose). Further it has the ability to scavenge the DPPH free radical efficiently (96.5 % scavenging at 200 µg/mL dose). Added to this the synthesized PJ-AgNPs displayed a very good mushroom tyrosinase inhibition at the tested concentrations. The above results indicate the potential of silver nanoparticles synthesized using PJ root extract can be used as an antibacterial, anti-biofilm, anti-oxidant, enzyme inhibitor in the food, medical and cosmetic industry.

In vitro and in vivo anti-pigmentation effects of 2-mercaptobenzimidazoles as nanomolar tyrosinase inhibitors on mammalian cells and zebrafish embryos: Preparation of pigment-free zebrafish embryos

Recently, 10 2-mercaptobenzo[d]imidazole (2-MBI) compounds (1–10) were synthesized. Although all 2-MBI compounds are tyrosinase inhibitors that inhibit mushroom tyrosinase at extremely low concentrations (IC50 values: 20–740 nM) and effectively inhibit the browning of apples, to our knowledge, no studies have determined whether 2-MBI compounds inhibit mammalian tyrosinase. Mammalian tyrosinase is different from mushroom tyrosinase in its distribution within the cell and has structural characteristics that are different from mushroom tyrosinase in amino acid sequence and in the presence of a quaternary structure. Thus, the effect of the 10 2-MBI compounds on mammalian tyrosinase activity was investigated in B16F10 cells. Six compounds (1–6) exhibited stronger intracellular tyrosinase inhibition than that of kojic acid and phenylthiourea (PTU), which are known to be the most potent tyrosinase inhibitors; their strong tyrosinase inhibitory activity robustly inhibited intracellular melanin production in B16F10 cells. None of the tested 2-MBI compounds exhibited appreciable cytotoxicity in HaCaT and B16F10 cells. To confirm the anti-melanogenic efficacy of the 2-MBI compounds in vivo, a zebrafish embryo model was used. At concentrations 100 times lower than kojic acid, most 2-MBI compounds demonstrated much stronger depigmentation efficacy than that of kojic acid, and three 2-MBI compounds (2–4) showed depigmentation activity similar to or more potent than that of PTU, resulting in nearly pigment-free zebrafish embryos. These results suggest that 2-MBI compounds may be potential therapeutic agents for hyperpigmentation-related disorders.

Design of potent tyrosinase inhibiting N-arylated-4-yl-benzamides bearing 2-aminothiazole-triazole bi-heterocycles: mechanistic insight through enzyme inhibition, kinetics and computational studies.

By using a convergent methodology, a unique series of N-arylated 4-yl-benzamides containing a bi-heterocyclic thiazole-triazole core was synthesized and the structures of these hybrid molecules, 9a-k, were corroborated through spectral analyses. The in vitro studies of these multi-functional molecules demonstrated their potent mushroom tyrosinase inhibition relative to the standard used. The kinetics mechanism was exposed by lineweaver-burk plots which revealed that, 9c, inhibited mushroom tyrosinase non-competitively by forming an enzyme-inhibitor complex. The inhibition constant Ki calculated from Dixon plots for this compound was 0.016 μM. The computational study was also consistent with the experimental results and these molecules disclosed good results of all scoring functions and interactions, which suggested a good binding to mushroom tyrosinase. So, it was predicted from the inferred results that these molecules might be considered as promising medicinal scaffolds for the diseases associated with the over-expression of this enzyme.

Thiazol-4(5H)-one analogs as potent tyrosinase inhibitors: synthesis, tyrosinase inhibition, antimelanogenic effect, antioxidant activity, and in silico docking simulation

As the β-phenyl-α,β-unsaturated carbonyl (PUSC) structure was previously identified to play a key role in tyrosinase inhibition, 14 analogs with a PUSC structure built on a thiazol-4(5H)-one scaffold were synthesized using Knoevenagel condensation to serve as potential tyrosinase inhibitors. Through mushroom tyrosinase inhibition experiments, two analogs 9 and 11 were identified as potent tyrosinase inhibitors, with 11 exhibiting an IC50 value of 0.4 ± 0.01 μM, which indicates its 26-fold greater potency than kojic acid. Kinetic studies using Lineweaver-Burk plots revealed that 9 and 11 are competitive and mixed-type inhibitors, respectively; these kinetic results were supported by docking simulations. According to the B16F10 cell-based experiments, 9 and 11 inhibited melanogenesis more effectively than kojic acid due to their potent cellular tyrosinase inhibitory activity. In addition, analogs 9 and 11 exhibited moderate-to-strong antioxidant capacity, scavenging ABTS+, DPPH, and ROS radicals. In particular, analog 12 with a catechol moiety exhibited very strong ROS-scavenging activity, similar to Trolox. These results suggest that analogs 9 and 11, which exhibit potent tyrosinase inhibitory activity in mushroom and mammalian cells and anti-melanogenic effects in B16F10 cells, are promising antibrowning agents for crops and skin lightening agents for hyperpigmentation-related diseases.

Methyl 4-pyridyl ketone thiosemicarbazone (4-PT) as an effective and safe inhibitor of mushroom tyrosinase and antibrowning agent

Enzymatic browning is of concern as it can affect food safety and quality. In this study, an effective and safe tyrosinase inhibitor and anti-browning agent, methyl 4-pyridyl ketone thiosemicarbazone (4-PT), was synthesised and characterised using Fourier-transform infrared (FTIR) spectroscopy, CHNS elemental analysis, and proton (1H) and carbon-13 (13C) nuclear magnetic resonance (NMR) spectroscopy. The vibrational frequencies of 4-PT were studied theoretically using vibrational energy distribution analysis (VEDA). Density functional theory (DFT) was applied to elucidate its chemical properties, including the Mulliken atomic charges, molecular electrostatic potential (MEP), quantum theory of atoms in molecules (QTAIM) and reduced density gradient non-covalent interactions (RDG-NCIs). Moreover, 4-PT was compared with kojic acid in terms of its effectiveness as a tyrosinase inhibitor and anti-browning agent. The toxicity and physicochemical properties of 4-PT were predicted via ADME evaluation, which proved that 4-PT is safer than kojic acid. Experimentally, 4-PT (IC50 = 5.82 μM, browning index (10 days) = 0.292 ± 0.002) was proven to be an effective tyrosinase inhibitor and anti-browning agent compared to kojic acid (IC50 = 128.17 μM, browning index (10 days) = 0.332 ± 0.002). Furthermore, kinetic analyses indicated that the type of tyrosinase inhibition is a mixed inhibition, with Km and Vmax values of 0.85 mM and 2.78 E-09 μM/s, respectively. Finally, the mechanism of 4-PT for tyrosinase inhibition was proven by 1D, second derivative and 2D IR spectroscopy, molecular docking and molecular dynamic simulation approaches.

Evaluation of antioxidant and anti-tyrosinase activities of surfactant and alcohol extracted Combretum Indicum leaves

Combretum Indicum (CI), which contains numerous bioactive compounds, has been used in traditional medicine for a variety of reasons, including the treatment of skin conditions. This study investigates the antioxidant and anti-tyrosinase activities of CI leaves extracted using different surfactants (Triton X-100 and Vitamin E TPGS) at concentrations of 1%, 2%, and 3%, as well as various alcohol solvents (acetone, methanol, and ethanol) at concentrations of 50%, 70%, and 90%. The antioxidant activity of the extracts has been evaluated using Total Phenolic Content (TPC) and 2,2-diphenyl-1-picrylhydrazyl (DPPH), while the anti-tyrosinase activity was assessed through a mushroom tyrosinase inhibition assay. Prior to analysis, CI leaves had been macerated, extracted, and freeze-dried. The research established that ethanol at a concentration of 50% is the optimum solvent to extract CI leaves, as it demonstrated good antioxidant and anti-tyrosinase action with a high percentage of yield and total phenolic content. As a result, the outcomes of this study contribute to a better understanding of the potential applications of CI leaf extract in cosmetics, notably in the treatment of oxidative stress and hyperpigmentation. Further study and development in this field could lead to the creation of effective and natural cosmetic products produced from CI leaves that have antioxidant and anti-tyrosinase effects.

In silico and in vitro studies of novel derivatives of tyrosol and raspberry ketone as the mushroom tyrosinase inhibitors.

Tyrosinase is the key enzyme for melanin biosynthesis. Overproduction and deposition of this pigment cause different problems in various industries including agriculture and food. Finding safe tyrosinase inhibitors thus attracts great research interest. The goal of this study is evaluation of inhibitory potencies of some novel synthetic derivatives of tyrosol and raspberry ketone on diphenolase activity of mushroom tyrosinase. The ligands inhibited enzyme activity and compound 4-(2-(4-(hydroxymethyl)-2-methyl-1,3-dioxolan-2-yl)ethyl)phenol (1d) exhibited the most inhibitory potency (77% inhibition, IC50=0.32µmol L-1) via the mixed inhibition mode. This compound was also safe according to the results of in vitro analyses. The enzyme-ligands interactions were theoretically and experimentally investigated using molecular docking and fluorescence quenching approaches, respectively. Modes of quenching and related parameters were also determined and molecular docking data showed that the ligands bind to important sites of the enzyme. These compounds, especially 1d, can be suggested as efficient candidates for further investigations.

Potent Antioxidant and Anti-Tyrosinase Activity of Butein and Homobutein Probed by Molecular Kinetic and Mechanistic Studies.

Butein (BU) and homobutein (HB) are bioactive polyhydroxylated chalcones widespread in dietary plants, whose antioxidant properties require mechanistic definition. They were investigated by inhibited autoxidation kinetic studies of methyl linoleate in Triton™ X-100 micelles at pH 7.4, 37 °C. Butein had kinh = (3.0 ± 0.9) × 104 M-1s-1 showing a chain-breaking mechanism with higher antioxidant activity than reference α-tocopherol (kinh = (2.2 ± 0.6) × 104 M-1s-1), particularly concerning the stoichiometry or peroxyl radical trapping n = 3.7 ± 1.1 vs. 2.0 for tocopherol. Homobutein had kinh = (2.8 ± 0.9) × 103 M-1s-1, pairing the relative BDEOH measured by radical equilibration EPR as 78.4 ± 0.2 kcal/mol for BU and estimated as 82.6 kcal/mol for HB. The inhibition of mushroom tyrosinase (mTYR) by HB and BU was also investigated. BU gives a reversible uncompetitive inhibition of monophenolase reaction with KI' = 9.95 ± 2.69 µM and mixed-type diphenolase inhibition with KI = 3.30 ± 0.75 µM and KI' = 18.75 ± 5.15 µM, while HB was nearly competitive toward both mono- and diphenolase with respective KI of 2.76 ± 0.70 µM and 2.50 ± 1.56 µM. IC50 values (monophenolase/diphenolase at 1 mM substrate) were 10.88 ± 2.19 µM/15.20 ± 1.25 µM, 14.78 ± 1.05 µM/12.36 ± 2.00 µM, and 33.14 ± 5.03 µM/18.27 ± 3.42 µM, respectively, for BU, HB, and reference kojic acid. Molecular docking studies confirmed the mechanism. Results indicate very potent antioxidant activity for BU and potent anti-tyrosinase activity for both chalcones, which is discussed in relation to bioactivity toward protection from skin disorders and food oxidative spoilage.

Evaluation of Rhodiola rosea Root Fraction as a Functional Cosmetic Ingredient

To develop functional cosmetic material using &lt;i&gt;Rhodiola rosea&lt;/i&gt;, the biological activities such as anti-oxidant, anti-inflammatory, astringent, anti-tyrosinase, and anti-elastase activity were investigated with methanol, &lt;i&gt;n&lt;/i&gt;-hexane, chloroform, ethyl acetate, n-butanol, and water fractions of &lt;i&gt;R. rosea&lt;/i&gt; Root. DPPH and ABTS radical scavenging activities of ethyl acetate fraction were increased in a dosedependent manner; the activities were higher than other fractions. The total phenolic content of ethyl acetate fraction also showed a relatively high value of 500.485±4.848 mgGAE/g. The ethyl acetate fraction also significantly decreased LPS-induced NO production and IL-6 secretion compared with untreated control cells at above 5-100 μg/mL concentrations. The astringent activity of ethyl acetate fraction was 94.31% at a concentration of 500 μg/mL, and the activity of ethyl acetate fraction was similar to that of tannic acid. The mushroom tyrosinase inhibition abilities of hexane, ethyl acetate, and butanol were 10.44%, 17.53%, and 14.55%, respectively, at 100 μg/mL. Furthermore, an elastase inhibition rate showed a relatively high effect at 100 μg/mL, 45.46% of inhibition rate in the ethyl acetate and 45.07% of inhibition rate in the butanol fraction. These results indicate that R. rosea Root would be used as a natural material in the functional cosmetic and beauty-food industries.

Exploring the Potential of ω3 Derivatives as Tyrosinase Inhibitors: A Comprehensive Study Combining Experimental, Computational, and Biological Approaches

AbstractIn this work, the inhibitory ability and mechanism of ω3‐nicotinic acid (ω3‐NA) and ω3‐Picolinic acid (ω3‐PA) complexes on the activity of mushroom tyrosinase (MT) were scrutinized for progressing a novel MT inhibitor. The complexes were synthesized. It was shown to have a considerable inhibition on the MT activity and Ki value of ω3‐NA and ω3‐PA on MT equal to 5.2 and 5.1 mM, respectively. ω3‐NA and ω3‐PA inhibited MT with Vmax values in the range of 0.134 mM and 0.14 mM, respectively. The outputs obtained from fluorescence quenching specified that ω3‐NA and ω3‐PA could interact with MT. Especially, the decrease in fluorescence intensity was due to the formation of a ligand‐enzyme complex which was mostly motivated by hydrogen bonding and hydrophobic forces. The presence of ω3‐NA and ω3‐PA altered the structure of MT and reduced the α‐helix of the enzyme. Molecular docking investigation along with molecular dynamics simulation exhibited that ligands‐MT formation is directed by hydrogen binding with Trp136, His263, and Val299 residues. The results highlight that ω3‐NA and ω3‐PA can be considered as possible inhibitors in treating hyperpigmentation via MT enzyme inhibition.

Heterocyclic Compounds as Synthetic Tyrosinase Inhibitors: Recent Advances.

Tyrosinase is a copper-containing enzyme which is widely distributed in nature (e.g., bacteria, mammals, fungi) and involved in two consecutive steps of melanin biosynthesis. In humans, an excessive production of melanin can determine hyperpigmentation disorders as well as neurodegenerative processes in Parkinson's disease. The development of molecules able to inhibit the high activity of the enzyme remain a current topic in medicinal chemistry, because the inhibitors reported so far present several side effects. Heterocycle-bearing molecules are largely diffuse in this sense. Due to their importance as biologically active compounds, we decided to report a comprehensive review of synthetic tyrosinase inhibitors possessing heterocyclic moieties reported within the last five years. For the reader's convenience, we classified them as inhibitors of mushroom tyrosinase (Agaricus bisporus) and human tyrosinase.

Synthesis, in silico modelling, and in vitro biological evaluation of substituted pyrazole derivatives as potential anti-skin cancer, anti-tyrosinase, and antioxidant agents

Twenty-five azole compounds (P1–P25) were synthesised using regioselective base-metal catalysed and microwave-assisted approaches, fully characterised by high-resolution mass spectrometry (HRMS), nuclear magnetic resonance (NMR), and infrared spectra (IR) analyses, and evaluated for anticancer, anti-tyrosinase, and anti-oxidant activities in silico and in vitro. P25 exhibited potent anticancer activity against cells of four skin cancer (SC) lines, with selectivity for melanoma (A375, SK-Mel-28) or non-melanoma (A431, SCC-12) SC cells over non-cancerous HaCaT-keratinocytes. Clonogenic, scratch-wound, and immunoblotting assay data were consistent with anti-proliferative results, expression profiling therewith implicating intrinsic and extrinsic apoptosis activation. In a mushroom tyrosinase inhibition assay, P14 was most potent among the compounds (half-maximal inhibitory concentration where 50% of cells are dead, IC50 15.9 μM), with activity greater than arbutin and kojic acid. Also, P6 exhibited noteworthy free radical-scavenging activity. Furthermore, in silico docking and absorption, distribution, metabolism, excretion, and toxicity (ADMET) simulations predicted prominent-phenotypic actives to engage diverse cancer/hyperpigmentation-related targets with relatively high affinities. Altogether, promising early-stage hits were identified – some with multiple activities – warranting further hit-to-lead optimisation chemistry with further biological evaluations, towards identifying new skin-cancer and skin-pigmentation renormalising agents.

Inhibitory Effects of Caulerpa racemosa, Ulva intestinalis, and Lobophora challengeriae on Tyrosinase Activity and α-MSH-Induced Melanogenesis in B16F10 Melanoma Cells.

Melanogenesis involves a synthesis of melanin pigment and is regulated by tyrosinase. The addition of whitening agents with tyrosinase-inhibiting properties in cosmetics is becoming increasingly important. In this study, the ethanolic extracts from twelve seaweeds were assessed for tyrosinase-inhibiting activity using mushroom tyrosinase and melanin synthesis in B16F10 melanoma cells. The highest mushroom tyrosinase inhibition (IC50) was observed with Lobophora challengeriae (0.15 ± 0.01 mg mL-1); treatment was more effective than kojic acid (IC50 = 0.35 ± 0.05 mg mL-1), a well-known tyrosinase inhibitor. Three seaweeds, Caulerpa racemosa, Ulva intestinalis, and L. challengeriae, were further investigated for their ability to reduce melanogenesis in B16F10 cells. The ethanolic extracts of C. racemosa, U. intestinalis, and L. challengeriae showed inhibitory effects by reducing melanin and intracellular tyrosinase levels in B16F10 cells treated with α-melanocyte stimulating hormone in a dose-dependent manner. C. racemosa (33.71%) and L. challengeriae (36.14%) at 25 µg mL-1 reduced melanin production comparable to that of kojic acid (36.18%). L. challengeriae showed a stronger inhibition of intracellular tyrosinase (decreased from 165.23% to 46.30%) than kojic acid (to 72.50%). Thus, ethanolic extracts from C. racemosa, U. intestinalis, and L. challengeriae can be good sources of natural tyrosinase inhibitors and therapeutic or cosmetic agents in the future.