Potent Tyrosinase Inhibitors Research Articles

Thioquinoline derivatives conjugated to thiosemicarbazide as potent tyrosinase inhibitors with anti-melanogenesis properties

In the present study, a series of aryl-substituted thioqunoline conjugated to thiosemicarbazide were rationally designed and synthesized. The formation of target compounds was confirmed by spectral characterization techniques such as IR, 1H-NMR, 13C-NMR, ESI–MS, and elemental analysis. Among the synthesized derivatives, compound 10g bearing para-chlorophenyl moiety was proved to be the most potent tyrosinase inhibitor with an IC50 value of 25.75 ± 0.19 µM. Compound 10g as the most potent derivative exhibited a noncompetitive inhibition pattern against tyrosinase in the kinetic study. Furthermore, the in silico cavity detection, as well as the molecular docking assessments, were performed to follow the behavior of 10g within the proposed binding site. Besides, the toxicity of 10g and its potency to reduce the melanin content on A375 cell lines were also measured. Consequently, aryl-substituted thioqunolines conjugated to thiosemicarbazide might be a promising candidate in the cosmetics, medicine, and food industry as tyrosinase inhibitors.

Synthesis and discovery of potential tyrosinase inhibitor of new coumarin-based thiophenyl-pyrazolylthiazole nuclei: In vitro evaluation, cytotoxicity, kinetic, and computational studies.

A well-known key enzyme in melanogenesis and hyperpigmentation is tyrosinase. The present study introduces a novel series of thiophenyl-pyrazolylthiazole-coumarin hybrids (6a-6h) as tyrosinase inhibitors. The in-vitro tyrosinase inhibition results indicated that all compounds have strong tyrosinase inhibitory activity, particularly compound 6g (IC50 = 0.043 ± 0.006 μM), was identified as the most active compound compared to the positive control (kojic acid, IC50 = 18.521 ± 1.162 μM). Lineweaver-Burk plots were employed to analyze the kinetic mechanism, and compound 6g formed an enzyme-inhibitor complex by inhibiting tyrosinase non-competitively. Furthermore, all compounds demonstrated excellent antioxidant activity against DPPH. MTT assay was used to screen the cytotoxicity of all compounds on B16F10 melanoma cells, and they had no toxic effect on the cells. The binding affinity of compounds with tyrosinase was also investigated using molecular docking, and the ligands displayed good binding energy values. These molecules could be a promising lead for skin pigmentation and associated diseases as nontoxic pharmacological scaffolds.

New insights into the inhibitory effect of phenol carboxylic acid antioxidants on mushroom tyrosinase by molecular dynamic studies and experimental assessment

The inhibitory effects of ferulic and chlorogenic acids on tyrosinase activity were investigated through multi-spectroscopic and molecular docking techniques. Ferulic and chlorogenic acids, flavonoid compounds, demonstrated inhibitory monophenolase activities of tyrosinase. The inhibitor effects against monophenolase activity were in a reversible and competitive manner with ki value equal to 6.8 and 7.5 µM respectively. The affinity between tyrosinase and L-DOPA decreased when fatty acids were added to the solution. The multi-spectroscopic techniques like UV-vis, fluorescence, and isothermal calorimetry are employed to investigate changes. Intrinsic fluorescence quenching and conformational changes of tyrosinase by hydrophobic interaction were confirmed. Tyrosinase had two and three binding sites for ferulic and chlorogenic acids with a binding constant in the order of magnitude of −6.8 and −7.2 kcal/mol. In addition, the secondary structural changes with Circular dichroism (CD) analysis, secondary structure (DSSP), radius of gyration (Rg) and analysis of hydrogen bonds (H-bonds) confirmed. Ferulic acid effect can be observed obviously and also content of α-helix decreased. Thermodynamic parameters indicated that the interaction between enzyme and ferulic and chlorogenic acids followed a spontaneous reaction dynamic manner with ΔG = −14.78 kJ/mol and ΔG = −14.61 kJ/mol (298k). The findings highlighted the potential applications of ferulic acid and chlorogenic acids in food and drug industries as potent inhibitors of tyrosinase. Communicated by Ramaswamy H. Sarma

Profiling of phytochemicals using LC-ESI-MS2 , in vitro, in vivo characterization and cosmeceutical effects of Alpinia galanga (wild) extract loaded emulgel.

The potential as a depigmenting agent, sun protection, and healthy benefits is indicated by the sun protection factor, radical scavenging, and tyrosinase inhibitory activities of Alpinia galanga (wild). A stable emulgel containing A .galanga (wild) extract is prepared. This emulgel is then characterized by in vitro evaluation and identification of contents by LC-ESI-MS2 . In vivo performance is counted in terms of moisturizing, melanin level, erythema, sebum, skin fine pores and large pores analysis, and other related physiological skin parameters. DPPH radical scavenging activity, total phenolic and flavonoid counts were used to measure the free radical scavenging and tyrosinase inhibitory capability of A .galanga (wild) extract, respectively. LC-ESI-MS2 used for phytochemical analysis. Emulgels synthesize, and their globule size, Ultracentrifugation, pH, and conductivity were all evaluated. Among the developed formulations, the optimal emulgels formulation underwent 90-day stability tests for organoleptic characteristics and rheology at 8°C, 25°C, 40°C, and 40°C + 75% RH (relative humidity). Using sebumeter®, mexameter®, and corneometer®, changes in skin physiological parameters were assessed over the course of 12 weeks in 13 healthy male, Asian volunteers. VisioFace® is used for computational analysis of high-resolution pictures to determine the % area, fine pore counts, and large pore counts of the skin. The antioxidant, tyrosinase inhibitory potential and counts of total phenolic and flavonoids of A .galanga (wild) extract were impressive (85%, 75%, and 48.0mg GAE/g and 14.37 mg quercetin/g, respectively). In terms of stability evaluation, globule size (0.7528 ± 0.192μm). Optimized A .galanga (wild) ethanol aqueous (AGEA) extract loaded emulgel was stable in terms of organoleptic and in vitro evaluation. The AGEA formulation significantly reduced the amount of sebum, erythema, fine pore counts, large pore counts, fine pore % area and large pores area percentage while significantly improved the moisture and elasticity of the skin. A stable A .galanga (wild) extract loaded emulgel was successfully produced that improved the skin physiological parameters in terms of skin's sebum, erythema, moisturizing, melanin, and pores.

2-Aminothiazole-Oxadiazole Bearing N-Arylated Butanamides: Convergent Synthesis, Tyrosinase Inhibition, Kinetics, Structure-Activity Relationship, and Binding Conformations.

A multi-step synthesis of novel bi-heterocyclic N-arylated butanamides was consummated through a convergent strategy and the structures of these medicinal scaffolds, 7a-h, were corroborated using spectral techniques. The in vitro analysis of these hybrid molecules revealed their potent tyrosinase inhibition as compared to the standard used. The kinetics mechanism was investigated through Lineweaver-Burk plots which exposed that, 7f, inhibited tyrosinase enzyme non-competitively by forming the enzyme-inhibitor complex. The inhibition constants Ki calculated from Dixon plots for this compound was 0.025 μM. Their binding conformations were ascertained by in silico computational studies whereby these molecules disclosed good binding energy values (kcal/mol). So, it was anticipated from the current research that these bi-heterocyclic butanamides might be probed as imperative therapeutic agents for melanogenesis.

Structural dynamics and susceptibility of isobutylamido thiazolyl resorcinol (ThiamidolTM) against human and mushroom tyrosinases

Tyrosinase, a key enzyme catalyzing a rate-limiting step of the melanin production, has been the most promising target for suppressing hyperpigmentation. Although a number of tyrosinase inhibitors have been developed, most of those lack clinical efficacy as they were identified from using mushroom tyrosinase (mTyr) as the target. Previous study revealed that the inhibitory effect of isobutylamido thiazolyl resorcinol (ThiamidolTM) on human tyrosinase (hTyr) is ∼100 times higher than that on mTyr. In the present study, we aimed to investigate the structural dynamics and susceptibility of ThiamidolTM against hTyr and mTyr at the atomic level using molecular docking, molecular dynamics simulation, and free energy calculation based on the molecular mechanics/Poisson-Boltzmann surface area method. The obtained results revealed that the resorcinol moiety of ThiamidolTM was found to be embedded in the catalytic copper center, interacting with H180, H202, H211, F386, and H390 residues of hTyr as well as with F264 residue of mTyr, mostly through van der Waals interactions. However, the number of destabilizing residues was found to be more pronounced in the ThiamidolTM/mTyr complex than the ThiamidolTM/hTyr system, supported by the lower binding affinity of ThiamidolTM/mTyr complex as well as the higher water accessibility and the lower number of atomic contacts at the active site of mTyr. Altogether, the structural and energetic information from this work would be useful for further optimization of more potent human tyrosinase inhibitors based on ThiamidolTM scaffold. Communicated by Ramaswamy H. Sarma

Antioxidant and Anti-Skin Aging Potential of Selected Thai Plants: In Vitro Evaluation and In Silico Target Prediction.

The skin is the largest organ that performs a variety of the body's essential functions. Impairment of skin structure and functions during the aging process might severely impact our health and well-being. Extensive evidence suggests that reactive oxygen species play a fundamental role in skin aging through the activation of the related degradative enzymes. Here, the 16 Thai medicinal plant species were screened for their potential anti-skin aging properties. All extracts were investigated for total phenolic and flavonoid contents, antioxidant, anti-elastase, and anti-tyrosinase activities, as well as the binding ability of compounds with target enzymes by molecular docking. Among all the plants screened, the leaves of A. occidentale and G. zeylanicum exhibited strong antioxidants and inhibition against elastase and tyrosinase. Other potential plants include S. alata leaf and A. catechu fruit, with relatively high anti-elastase and anti-tyrosinase activities, respectively. These results are also consistent with docking studies of compounds derived from these plants. The inhibitory actions were found to be more highly positively correlated with phenolics than flavonoids. Taken together, our findings reveal some Thai plants, along with candidate compounds as natural sources of antioxidants and potent inhibitors of elastase and tyrosinase, could be developed as promising and effective agents for skin aging therapy.

Extracts from European Propolises as Potent Tyrosinase Inhibitors.

Tyrosinase is a key enzyme in the melanogenesis pathway. Melanin, the product of this process, is the main pigment of the human skin and a major protection factor against harmful ultraviolet radiation (UVR). Increased melanin synthesis due to tyrosinase hyperactivity can cause hyperpigmentation disorders, which in consequence causes freckles, age spots, melasma, or postinflammatory hyperpigmentation. Tyrosinase overproduction and hyperactivity are triggered by the ageing processes and skin inflammation as a result of oxidative stress. Therefore, the control of tyrosinase activity is the main goal of the prevention and treatment of pigmentation disorders. Natural products, especially propolis, according to their phytochemical profile abundant in polyphenols, is a very rich resource of new potential tyrosinase inhibitors. Therefore, this study focused on the assessment of the tyrosinase inhibitory potential of six extracts obtained from the European propolis samples of various origins. The results showed the potent inhibitory activity of all tested propolis extracts towards commercially available mushroom tyrosinase. The four most active propolis extracts showed inhibitory activity in the range of 86.66-93.25%. Apart from the evaluation of the tyrosinase inhibition, the performed research included UHPLC-DAD-MS/MS (ultra high performance liquid chromatography coupled with diode array detection and tandem mass spectrometry) phytochemical profiling as well as antioxidant activity assessment using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the 2,2"-azino-bis(3-ethylbenzothiazoline-6-sulfuric acid (ABTS) radical scavenging tests. Moreover, statistical analysis was used to correlate the tyrosinase inhibitory and antioxidant activities of propolis extracts with their phytochemical composition. To summarise, the results of our research showed that tested propolis extracts could be used for skin cosmeceutical and medical applications.

Elucidating the Role of Santalol as a Potent Inhibitor of Tyrosinase: In Vitro and In Silico Approaches.

This research work focuses on the potential application of an organic compound, santalol, obtained from santalum album, in the inhibition of the enzyme tyrosinase, which is actively involved in the biosynthesis of melanin pigment. Over-production of melanin causes undesirable pigmentation in humans as well as other organisms and significantly downgrades their aesthetic value. The study is designed to explain the purification of tyrosinase from the mushroom Agaricus bisporus, followed by activity assays and enzyme kinetics to give insight into the santalol-modulated tyrosinase inhibition in a dose-dependent manner. The multi-spectroscopic techniques such as UV-vis, fluorescence, and isothermal calorimetry are employed to deduce the efficiency of santalol as a potential candidate against tyrosinase enzyme activity. Experimental results are further verified by molecular docking. Santalol, derived from the essential oils of santalum album, has been widely used as a remedy for skin disorders and a potion for a fair complexion since ancient times. Based on enzyme kinetics and biophysical characterization, this is the first scientific evidence where santalol inhibits tyrosinase, and santalol may be employed in the agriculture, food, and cosmetic industries to prevent excess melanin formation or browning.

Evaluation of the Antioxidant, Cytoprotective and Antityrosinase Effects of Schisandra chinensis Extracts and Their Applicability in Skin Care Product.

Plant extracts have been widely used for skin care for many centuries, and nowadays, they are commonly applied for the development and enrichment of new cosmetic preparations. The present study aimed the assessment of the biological activity of aqueous Schisandra chinensis extracts as a potential ingredient of skin care products. The aspects studied involved the ability to neutralize free radicals, impact on viability and metabolism of keratinocytes, as well as tyrosinase inhibitory potential. Our study showed that aqueous S. chinensis extracts have a positive effect on keratinocyte growth and have high antioxidant potential and strong tyrosinase inhibitory activity. UPLC-MS analysis revealed that three groups of phenolic compounds were predominant in the analyzed extract, including lignans, phenolic acids and flavonoids and protocatechiuc and p-coumaryl quinic acids were predominant. Moreover, microwave-assisted extraction, followed by heat reflux extraction, was the most effective for extracting polyphenols. Furthermore, a prototypical natural body washes gel formulation containing the previously prepared extracts was developed. The irritation potential and viscosity were assessed for each of the formulations. The study demonstrated that the addition of these extracts to body wash gel formulations has a positive effect on their quality and may contribute to a decrease in skin irritation. In summary, S. chinensis aqueous extracts can be seen as an innovative ingredient useful in the cosmetic and pharmaceutical industry.

Investigation of phenyllactic acid as a potent tyrosinase inhibitor produced by probiotics

Melanogenesis is responsible for skin pigmentation and the enzymatic browning of foods. Tyrosinases play a major role in melanin synthesis, and many attempts have been made to identify new natural tyrosinase inhibitors, but few have sought to do in microbes. Postbiotics are bioactive compounds produced by the metabolism of probiotics and have been reported to be safe and effective. In this study, we evaluated the tyrosinase inhibitory effects of culture supernatants of probiotics and discovered novel bacterial metabolites that can be used as a potent tyrosinase inhibitor based on metabolomics. Cultures of Bifidobacterium bifidum IDCC 4201 and Lactiplantibacillus plantarum IDCC 3501 showed effective anti-tyrosinase, reduced melanin synthesis, and altered protein expression associated with the melanogenesis pathway. Comparative metabolomics analyses conducted by GC-MS identified metabolites commonly produced by B. bifidum and L. plantarum. Of eight selected metabolites, phenyllactic acid exhibited significant tyrosinase-inhibitory activity. Our findings suggest that applications of probiotic culture supernatants containing high amounts of phenyllactic acid have potential use as anti-melanogenesis agents in food and medicines.

Biotechnological exploration of Carthamus tinctorius as apromising approach for cosmeceuticals: Phytochemical, biological, and micro-emulgel formulation development studies

• Carthamus tinctorius is a medicinal plant known to possess different traditional uses. • Seed extract of the plant were screened for phytochemical analysis, antioxidant, and anti-tyrosinase activities. • The studied extract was found to contain considerable bioactive compounds and biological potential. • The micro-emulgel of plant extract was formulated and characterized by different standard in-vitro paraments. The micro-emulgel (MEG) loaded with natural plant extracts can be a promising innovative technique for cosmetology as the use of plant-based phytochemicals is gaining popularity day by day in the field. So, the present study was meant to formulate, characterize, and evaluate plant extract-based (seeds of Carthamus tinctorius, CT ) polyphenol-loaded MEG. Assessment of the plant extract for antioxidant potential was made by DPPH and reducing power assay, total phenolic and flavonoid contents, tyrosinase inhibition potential, polyphenolic profiling by HPLC and was subjected to formulate a stable MEG system; further assessed by stability studies of three months by zeta analysis (zeta sizing and potential), polydispersity index and release of phytoconstituents using static Franz-diffusion cell. Results revealed that CT extract is constituted of several polyphenols with high antioxidant and tyrosinase inhibitory potential. Moreover, the developed micro-emulsion is stable at various storage conditions with promising zeta size, zeta potential, and PDI values of 216.6 nm, -18 mV, and 0.442, respectively. 86.64% release from micro-emulsion was observed in comparison to 47.60% release from MEG. Conclusively, CT -based polyphenol-loaded stable MEG could be potentially employed as an improved vehicle for cosmeceutical purposes than conventional formulations.

Computational Analysis of Triazole-Based Kojic Acid Analogs as Tyrosinase Inhibitors by Molecular Dynamics and Free Energy Calculations

Molecular docking, molecular dynamics (MD) simulations and the linear interaction energy (LIE) method were used here to predict binding modes and free energy for a set of 1,2,3-triazole-based KA analogs as potent inhibitors of Tyrosinase (TYR), a key metalloenzyme of the melanogenesis process. Initially, molecular docking calculations satisfactorily predicted the binding mode of evaluated KA analogs, where the KA part overlays the crystal conformation of the KA inhibitor into the catalytic site of TYR. The MD simulations were followed by the LIE method, which reproduced the experimental binding free energies for KA analogs with an r2 equal to 0.97, suggesting the robustness of our theoretical model. Moreover, the van der Waals contributions performed by some residues such as Phe197, Pro201, Arg209, Met215 and Val218 are responsible for the binding recognition of 1,2,3-triazole-based KA analogs in TYR catalytic site. Finally, our calculations provide suitable validation of the combination of molecular docking, MD, and LIE approaches as a powerful tool in the structure-based drug design of new and potent TYR inhibitors.

Anti-tyrosinase and antioxidant activity of meroterpene bakuchiol from Psoralea corylifolia (L.)

Bakuchiol is gaining major interest for treatments against skin photoaging. The kinetics of mushroom tyrosinase inhibition by bakuchiol, by real-time oxygen sensing and UV–vis monitoring (475 nm), showed competitive inhibition with average Ki constant (µM, 30 °C, pH 6.8) of 6.71 ± 1.23 and 1.15 ± 0.34 for monophenolase and diphenolase reactions respectively, with respective IC50 37.22 ± 5.18 and 6.91 ± 0.96 ∼ at 1 mM substrate, compared to kojic acid IC50 34.02 ± 5.51 and 16.86 ± 3.28 μM. Fluorescence quenching showed a single binding mode with formation constant Ka 1.02 × 106 M−1. The antioxidant activity was studied by inhibited autoxidation of styrene and cumene (PhCl, 30 °C) affording inhibition constant kinh = 18.1 ± 6.6 (104M−1s−1, 30 °C) and of MeLin in Triton™ X-100 micelles giving kinh = 0.16 ± 0.03 (104M−1s−1, 37 °C). Stoichiometric factor was 1.9 ± 0.1. ReqEPR spectroscopy afforded the BDE(OH) as 81.7 ± 0.1 kcal/mol. Bakuchiol is a potent tyrosinase inhibitor with good antioxidant activity having major potential as natural food preservative against oxidation and food-browning.

Synthesis and biological evaluation of substituted aurone derivatives as potential tyrosinase inhibitors: in vitro, kinetic, QSAR, docking and drug-likeness studies

Tyrosinase enzyme plays an essential role in melanin biosynthesis and enzymatic browning of fruits and vegetables. To discover potent tyrosinase inhibitors, the present studies were undertaken. In this context, synthetic aurone derivatives 26–50 were designed, synthesized, and structurally elucidated by various spectroscopic techniques including IR, UV, 1H- & 13C-NMR and mass spectrometry. The target compounds 26–50 were screened for their anti-tyrosinase inhibitory potential, and thus kinetic mechanism was analyzed by Lineweaver-Burk plots. All target compounds exhibited good to excellent IC50 values in the range of 7.12 ± 0.32 μM to 66.82 ± 2.44 μM. These synthesized aurone derivatives were found as potent tyrosinase inhibitors relative to the standard kojic acid (IC50 = 16.69 ± 2.81 μM) and the compound 39 inhibited tyrosinase non-competitively (Ki = 11.8 μM) by forming an enzyme-inhibitor complex. The binding modes of these molecules were ascribed through molecular docking studies against tyrosinase protein (PDB ID: 2Y9X). The quantitative structure-activity relationship studies displayed a good correlation between 26–50 structures and their anti-tyrosinase activity (IC50) with a correlation coefficient (R2) of 0.9926. The computational studies were coherent with experimental results and these ligands exhibited good binding values against tyrosinase and interacted with core residues of target protein. Moreover, the drug-likeness analysis also showed that some compounds have a linear correlation with Lipinski’s rule of five, indicating good drug-likeness and bioactivity scores for pharmacological targets. Communicated by Ramaswamy H. Sarma

Investigating Potential Cardiovascular Toxicity of Two Anti-Leukemia Drugs of Asciminib and Ponatinib in Zebrafish Embryos.

BCR-ABL, a fusion protein kinase, is a druggable target exclusively expressed in patients with chronic myeloid leukemia (CML). Several anti-leukemia medicines targeting this protein have been developed in recent years. However, therapeutic options are limited for CML patients bearing multiple BCR-ABL1 mutations. Ponatinib (PON), a potent tyrosinase inhibitor, was one of the approved drugs for managing BCR-ABL1 T315I mutant disease. However, treatment of patients with PON reported severe side effects related to cardiovascular events. Asciminib (ASC) was the first allosteric inhibitor approved to target the myristoyl pocket of BCR-ABL protein to inhibit protein activity. The different mechanism of inhibition opens the possibility of co-exposure with both medicines. Reports on cardiovascular side effects due to the combination use of PON + ASC in pre-clinical and clinical studies are minimal. Thus, this study aimed to observe the potential cardiovascular-related side effect after co-exposure to ASC and PON using zebrafish as an animal model. In this study, zebrafish were acutely exposed to both compounds. The cardiovascular physiology parameters and gene expression related to cardiovascular development were evaluated. We demonstrate that combining ASC with PON at no observed effect concentration (NOEC) did not cause any significant change in the cardiac performance parameter in zebrafish. However, a significant increase in nkx2.5 expression level and a substantial decrease in blood flow velocity were recorded, suggesting that combining these compounds at NOEC can cause mild cardiovascular-related side effects.

Elderberry (Sambucus nigra L.) wine as a novel potential functional food product

Throughout human civilization, elderberry (Sambucus nigra L.) has been used as a traditional drug and addition to various dishes. Although it is a widespread plant species, it is still being researched and rarely used to obtain new products. In this study, we focused on the chemical and phytochemical composition and biological and pharmacological effects of elderberry wine, obtained by applying different temperature treatments (without temperature treatment – W1; 60 °C, 5 min – W2; 60 °C, 10 min – W3; and 70 °C, 5 min – W4). HPLC-MS/MS and spectrophotometric techniques determined the chemical and phytochemical profiles of obtained wines. The main compounds in analyzed wines were p-Hydroxybenzoic, protocatechuic and chlorogenic acids, quercetin, quercetin-3-O-hexoside, and rutin. To assess the biological potential, antioxidant, neuroprotective (acetyl- and butyrylcholinesterase inhibition), antityrosinase, and antidiabetic (amylase inhibition and glucosidase inhibition) abilities were examined. Wine W4 showed the strongest antioxidant activity, which correlated well with the high phenol content. The best inhibitory effect of β-glucosidase was observed in wine W3. However, the most potent tyrosinase inhibitor was wine W4. The presented results prove elderberry wine's high biological and industrial potential and open new avenues for formulating new products that could be brought to market.

Screening and identification of tyrosinase inhibitors in edible plant materials by on-line UPLC-enzyme reactor coupled with UHPLC-FTMS

Tyrosinase plays a primary role in melanin biosynthesis and enzymatic browning of freshly cut fruits and vegetables. Herein, an on-line ultraperformance liquid chromatography diode array detector biochemical detection (UPLC-DAD-BCD) method was established to identify trace amount potent tyrosinase inhibitors and antibrowning agents in complex mixtures. The tyrosinase inhibition activities of some representative compounds were evaluated by using the established method and their chromatography-activity relationships were obtained. Then the proposed UPLC-DAD-BCD method was applied to screen tyrosinase inhibitors in edible herbal extracts and identified two tyrosinase inhibitors in green tea and three in cinnamon. The above active ingredients were determined by ultra-high-performance liquid chromatography linear ion trap/orbitrap high resolution mass spectrometry (UHPLC-FTMS). The on-line UPLC-DAD-BCD in combination with UHPLC-FTMS was confirmed to be a powerful technique to screen and elucidate the active ingredients in complex matrixes and could be applied to evaluate the integrated effects of multiple ingredients against corresponding targets.

The Influence of Different Extraction Techniques on the Chemical Profile and Biological Properties of Oroxylum indicum: Multifunctional Aspects for Potential Pharmaceutical Applications.

Oroxylum indicum (L.) Kurz (Bignoniaceae), a traditional Chinese herbal medicine, possesses various biological activities including antioxidant, anti-inflammatory, antibacterial, and anticancer. In order to guide the practical application of O. indicum in the pharmaceutical, food, and cosmetic industries, we evaluated the effects of five different extraction techniques (maceration extraction (ME), oxhlet extraction (SOXE), ultrasound-assisted extraction (UAE), tissue-smashing extraction (TSE), and accelerated-solvent extraction (ASE)) with 70% ethanol as the solvent on the phytochemical properties and biological potential. The UHPLC-DAD Orbitrap Elite MS technique was applied to characterize the main flavonoids in the extracts. Simultaneously, the antioxidant and enzyme inhibitory activities of the tested extracts were analyzed. SOXE extract showed the highest total phenolic content (TPC, 50.99 ± 1.78 mg GAE/g extract), while ASE extract displayed the highest total flavonoid content (TFC, 34.92 ± 0.38 mg RE/g extract), which displayed significant correlation with antioxidant activity. The extract obtained using UAE was the most potent inhibitor of tyrosinase (IC50: 16.57 ± 0.53 mg·mL−1), while SOXE extract showed the highest activity against α-glucosidase (IC50: 1.23 ± 0.09 mg·mL−1), succeeded by UAE, ME, ASE, and TSE extract. In addition, multivariate analysis suggested that different extraction techniques could significantly affect the phytochemical properties and biological activities of O. indicum. To sum up, O. indicum displayed expected biological potential and the data collected in this study could provide an experimental basis for further investigation in practical applications.

Design, synthesis, in vitro, and in silico studies of novel benzylidene 6-methoxy-1-tetralone linked to benzyloxy and benzyl -1,2,3- triazole rings as potential tyrosinase inhibitors

Novel benzylidene 6-methoxy-1-tetralone derivatives linked to benzyloxy- and benzyl -1,2,3- triazole rings were designed, synthesized, and evaluated as potential tyrosinase inhibitors. The products can be divided into two groups: Benzyloxy-benzylidene-6-methoxy-1-tetralone and Benzyl-1,2,3-triazole-benzylidene-6-methoxy-1-tetralone derivatives. Some of them showed acceptable activities against mushroom tyrosinase enzyme. Among them, (E)-2-(4-((1-(3-chlorobenzyl)-1H-1,2,3-triazol-4-yl)methoxy)-3-methoxybenzylidene)-6-methoxy-3,4-dihydronaphthalen-1(2H)-one (7d) containing 1,2,3-triazole ring and 3-chlorine at the benzyl pendant moiety indicated significant anti-tyrosinase activity with an IC50 value of 4.64 μM which was better inhibitory activity than kojic acid as reference compound (19.26 μM). The molecular modeling studies demonstrated that the compound 7d could occupy the adjacent pocket to the binding site. Compound 7d interacted with the loop (Ile184-Asp191) through its 6-methoxy-3,4-dihydronaphthalen-1(2H)-one moiety that oriented the 3-clorophenyl group to the entrance of binding site. Kinetics study showed compound 7d acts as an uncompetitive inhibitor and molecular modeling conformed results. In silico ADMET studies predicted that these products have good drug-likeness. All findings indicate that compound 7d has good potential for the inhibition of melanogenesis compared to kojic acid.