Tyrosinase Inhibitory Effects Research Articles

An integrated in silico and in vitro approach for the identification of natural products tyrosinase inhibitors

The biosynthesis of melanin, the main protein involved in skin pigmentation, involves tyrosine, the enzyme tyrosinase, and ultraviolet radiation. However, an imbalance in this process can promote cutaneous hypermelanosis (CH), which causes spots on the skin. The CH treatment involves techniques and products with high adverse reactions. In this context, research has been increased into natural products. However, investigations using computational tools combined with evaluations of enzyme inhibition (in vitro) and toxicity tests are scarce. In this study, we evaluated thirteen bioactive compounds using virtual screening (SwissADME and SwissTarget Prediction software), and the most promising molecules were tested for tyrosinase inhibitory effects and cytotoxicity assays (MTT). Kaempferol, apigenin, and quercetin revealed better in silico bioavailability and tyrosinase inhibition parameters (94.8, 91.9, and 88.4%, respectively). Additionally, these molecules demonstrated different cytotoxicity profiles at 24 and 48 hours of exposure. Our evidence indicates that the flavonoids tested are promising agents in inhibiting tyrosinase.

Nitrophenylpiperazine derivatives as novel tyrosinase inhibitors: design, synthesis, and in silico evaluations

A novel series of 4-nitrophenylpiperazine derivatives (4a–m) was designed and synthesized as potential tyrosinase inhibitors. Comprehensive characterization using 1H-NMR, 13C-NMR, CNH, and IR techniques was performed for all target compounds. Subsequently, the derivatives were evaluated for their inhibitory activity against tyrosinase. Among them, compound 4l, featuring an indole moiety at the N−1 position of the piperazine ring, exhibited a significant tyrosinase inhibitory effect with an IC50 value of 72.55 μM. Enzyme kinetics analysis revealed that 4l displayed mixed inhibition of the tyrosinase enzymatic reaction. Molecular docking was carried out in the enzyme’s active site to further investigate the enzyme-inhibitor interactions. Based on the findings, compound 4l shows promise as a lead structure for the design of potent tyrosinase inhibitors. This study paves the way for the development of more effective tyrosinase inhibitors for potential applications in various fields.

Cumin (Cuminum cyminum L.) an export-oriented Indian seed spice with inherent nutraceutical and therapeutic attributes: A review

Cumin seeds and value-added products are used in beverages, liquors,candy, nutraceuticals, therapeutics, toiletries, perfumery and lotions. In theIndian systems of medicine, cumin finds a vital role through its essential &total oil components and various aqueous and alcoholic extracts. Cuminseeds contain volatile oil (3–4%), the primary active principles of which arecumin aldehyde, terpenes (45–50%), phenols, unsaturated and saturatedfatty acids, etc., those occur in varying fractions compensating each other,which act as a scavenger for free radicals and antioxidants. As anutraceutical, cumin seeds contain plenty of iron, magnesium, calcium,manganese, and phosphorus. The vitamins present include thiamine,riboflavin, niacin, vitamin A, C, E, K, and vitamin B6. The seedspossessdiuretic, carminative, stimulant, digestive, tonic, appetizer, stomachic andastringent properties. It is traditionally an essential critical remedial agentfor digestion, diarrhoea, leucorrhoea, eczema, atonic, flatulence,dyspepsia and abdominal pains. Phytochemicals like alkaloid, coumarin,anthraquinone, flavonoid, protein, glycoside, resin, saponin, tannin andsteroids are abundant in its seed. Cumin seed extracts bear variousmedicinal properties such as insecticidal, antimicrobial, anti-inflammatory,antioxidant, antidiabetic, anticancer, hypotensive, bronchodilator,immunological, contraceptive, aldose reductase, analgesic,alpha-glucosidase and tyrosinase inhibitory effects, etc. Thus use of cumin offerscombined advantages, providing both nutraceutical and therapeuticproperties simultaneously.

Anti-melanogenic effect of <i>Amaranthus tricolorextract</i> on UV radiation-exposed melanoma cells

Purpose: To determine the inhibitory effect of A. tricolor extract (ATE) on melanogenesis in UV radiation-exposed B16F10 cells. 
 Methods: Total phenolic and anthocyanin contents of ATE were examined by Folin-Ciocalteu and pH differential methods, respectively. The tyrosinase inhibitory effect of ATE was investigated using L-DOPA as a substrate and the suppressive effect of ATE on melanin production was determined in melanoma cells. Furthermore, the antioxidant activity was assessed by DPPH method and reactive oxygen species formation while protein expression levels were evaluated by western blot method. 
 Results: The total phenolic and anthocyanin contents were identified up to 35 mg/g extract and 0.85 mg/g extract, respectively. ATE was found to inhibit both mushroom and cellular tyrosinase at IC50 values of 242.2 ± 9.5 μg/mL and 202.9 ± 11.6 μg/mL, respectively. Moreover, ATE treatment reduced melanin production up to (30 ± 5) % and suppressed p38 MAPK phosphorylation at the concentration of 400 μg/mL. In addition, ATE significantly scavenged DPPH radical with EC50 value of 189.2 ± 8.9 μg/mL and abolished ROS formation in the cells. 
 Conclusion: These results indicate that A. tricolor extract has a potential protective effect against melanin production, suggesting its potential value in skin-lightening formulations.

Six unprecedented 2-(2-phenethyl)chromone dimers from agarwood of Aquilaria filaria

Six new dimeric 2-(2-phenylethyl)chromones (1–6) were successfully isolated from the ethanol extract of agarwood of Aquilaria filaria from Philippines under HPLC-MS guidance. Compounds 1–6 are all dimers formed by linking 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromone and flindersia 2-(2-phenylethyl)chromone via a single ether bond, and the linkage site (C5-O-C8′′) of compound 2 is extremely rare. A variety of spectroscopic methods were used to ascertain their structures, including extensive 1D and 2D NMR spectroscopic analysis, HRESIMS, and comparison with literature. The in vitro tyrosinase inhibitory and anti-inflammatory activities of each isolate were assessed. Among these compounds, compound 2 had a tyrosinase inhibition effect with an IC50 value of 27.71 ± 2.60 μM, and compound 4 exhibited moderate inhibition of nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cells with an IC50 value of 35.40 ± 1.04 μM.

Cassia angustifolia Vahl. Leaves: Determination of Total Phenolic and Sennoside Contents of Different Fractions in Comparison with Their α- Glucosidase and Tyrosinase Inhibitory Effects

Background: Cassia angustifolia Vahl. (Senna) is a medicinal plant containing anthraquinone compounds such as sennoside. Senna is primarily valued for its laxative properties. In Persian medicine, this plant has been also used to treat various disorders such as diabetes and skin hyperpigmentation. Previous studies have shown that different species of senna, such as C. articulata, C. alata, C. Siamea, C. Surattensis inhibit alpha-amylase and α-glucosidase enzymes. To the best of our knowledge, no previous evidence is available on tyrosinase and α-glucosidase inhibitory effects of the extract and different fractions of C. angustifolia leaves. Objectives: The purpose of this study was to investigate the inhibitory effect of the methanol-water extract and different fractions (hexane, chloroform, ethyl acetate, and remaining crude extract) of senna against tyrosinase and α-glucosidase and to investigate their total phenolic and sennoside B contents. Results: Our findings depicted that the methanol-water extract and fractions had no significant anti-tyrosinase activity; however, some fractions were active toward α-glucosidase. The hexane fraction and the remaining crude extract demonstrated the highest inhibition on α-glucosidase compared to acarbose (positive control). In addition, the ethyl acetate fraction contains high phenolic and hydroxy anthraquinone derivatives based on the amount of sennoside B contents equivalent to 382.25 μg/mL of gallic acid and 1.525% of sennoside B, respectively. Moreover, no correlation was observed between the phenolic and sennoside contents of different fractions and their α-glucosidase inhibitory effect. Conclusions: Considering the α-glucosidase inhibition results, the hexane fraction of C. angustifolia can be a valuable fraction for in vitro and in vivo antidiabetic studies as well as further phytochemical studies. Further studies to identify the active substances and the exact mechanism of the bioactive ingredients on the inhibitory effects of α-glucosidase can provide promising results in the future.

Novel Dihydrocoumarins Induced by Radiolysis as Potent Tyrosinase Inhibitors.

A representative naturally occurring coumarin, 4-methylumbelliferone (5), was exposed to 50 kGy of gamma ray, resulting in four newly generated dihydrocoumarin products 1-4 induced by the gamma irradiation. The structures of these new products were elucidated by interpretation of spectroscopic data (NMR, MS, [α]D, and UV). The unusual bisdihydrocoumarin 4 exhibited improved tyrosinase inhibitory capacity toward mushroom tyrosinase with IC50 values of 19.8 ± 0.5 μM as compared to the original 4-methylumbelliferone (5). A kinetic analysis also exhibited that the potent metabolite 4 had non-competitive modes of action. Linkage of the hydroxymethyl group in the C-3 and C-4 positions on the lactone ring probably enhances the tyrosinase inhibitory effect of 4-methylumbelliferone (5). Thus, the novel coumarin analog 4 is an interesting new class of tyrosinase inhibitory candidates that requires further examination.

Isolation, characterization and evaluation of oxypeucedanin and osthol from local endemic Prangos aricakensis Behçet and Yapar root as antioxidant, enzyme inhibitory, antibacterial and DNA protection: molecular docking and DFT approaches

Prangos species were previously used against many disorders due to their chemical component. Prangos aricakensis Behçet & Yapar is a newly discovered local endemic species in Turkey’s eastern region, and there is no research on P. aricakensis in the literature. In this work, oxypeucedanin and osthol molecules have been isolated from the root part of P. aricakensis for the first time. Oxypeucedanin and osthol structures were elucidated by 1D and 2D NMR analysis. For the bioactivities determination, antioxidant (DPPH· and ABTS·+ scavenging), enzyme inhibition (AChE, BChE, tyrosinase, and urease), antibacterial and DNA protection activity studies were applied for both molecules and compared with standard drug molecules, after applying enzyme kinetic assays and in silico approaches to clarify the mechanism of action for both molecules with enzymes, using molecular docking and density functional theory (DFT). Oxypeucedanin (2.19 ± 0.38 µg/mL) and osthol (4.57 ± 1.28 µg/mL) exhibited better activity than standards in DPPH∙ scavenging activity. Osthol (11.76 ± 0.59 µg/mL) showed a better tyrosinase inhibition effect than kojic acid (12.82 ± 0.91 µg/mL), and oxypeucedanin (3.03 ± 0.01 µg/mL) showed better urease inhibition effect than thiourea (5.37 ± 1.86 µg/mL). Our results showed that the osthol molecule was an excellent skin protective agent while the oxypeucedanin molecule could be a remarkable antiulcer agent. Therefore, although this study is the first in its field, it remained in the in vitro and in silico stages and is thought to pave the way for in vivo studies in the future. Communicated by Ramaswamy H. Sarma

Essential Oils From the Trunks and Leaves of Paramignya scandens (Griff.) Craib From Vietnam: Phytochemical Composition, In Vitro α-Amylase and Tyrosinase Inhibitory Activities and In Silico Molecular Docking Studies

Objective/Background: This work aims to evaluate the chemical composition of Paramignya scandens essential oils (EOs), their in vitro α-amylase, tyrosinase inhibitory activities, and in silico molecular docking study. Methods: The EOs of P scandens trunks and leaves were extracted by hydrodistillation process and the chemical compositions were determined by gas chromatography-mass spectrometry. These EOs were also tested for in vitro α-amylase and tyrosinase inhibitory activities. Additionally, in silico molecular docking simulations on the main components of the EOs were performed. Results: The EO profiles of P scandens trunks and leaves included 21 (98.8%) and 34 (89.7%) components, respectively. The main compounds in the trunk EO were ( E)- β-caryophyllene (60.8%), α-humulene (13.0%), and germacrene D (7.4%). The predominant compounds of the leaf EO were caryophyllene oxide (16.7%), ( E) -β-caryophyllene (14.6%), spathulenol (12.2%), germacrene D (6.5%), and α-humulene (5.0%). Moreover, their α-amylase and tyrosinase inhibitory effects were demonstrated for the first time. In molecular docking results, ( E)- β-caryophyllene was the potential compound in EOs with the best binding affinity against the α-amylase enzyme, whereas spathulenol revealed the strongest binding ability with the tyrosinase enzyme. Furthermore, the assessment of potential interactions between the main components of the EOs and the selected proteins was elucidated. Conclusions: The results of this work revealed that EOs of P scandens trunks and leaves had α-amylase and tyrosinase inhibition properties and potential applications in nutraceuticals, medicine, and cosmetics.

6‐(Hydroxymethyl)‐8‐oxo‐4,8‐dihydropyrano[3,2‐b]pyrans as New Tyrosinase Inhibitors and Antioxidant Agents

AbstractA series of ethyl 2‐amino‐6‐(hydroxymethyl)‐8‐oxo‐4,8‐dihydropyrano[3,2‐b]pyran‐3‐carboxylates (P1‐P13) as annulated kojic acid derivatives were synthesized, and evaluated for their tyrosinase inhibitory activity as well as radical scavenging effect. It was found that derivatives P6 and P9, bearing 3‐chlorophenyl and 4‐hydroxy‐3,5‐dimethoxyphenyl at the C4 position, possessed good tyrosinase inhibitory effects with IC50 values of 52.1±2.3 and 80.7±2.5 μM, respectively. Compound P9 also exhibited remarkable free radical scavenging activity with an EC50 value of 15.3±3.1 μM compared to the standard ascorbic acid (EC50=21.6±1.9 μM). The results of molecular docking analysis exposed that P6 and P9 bind well with the active site of tyrosinase mainly by hydrogen bonds and hydrophobic interactions. In silico studies showed that these molecules fulfilled drug‐likeness rules and possessed acceptable predictive absorption, distribution, metabolism, and excretion features. This study could provide new ideas for developing effective tyrosinase inhibitors and antioxidant agents.

Electroanalytical Investigation of 2‐(2‐Methylbenzyl)‐4(7)‐phenyl‐1H‐benzo[d]imidazole, a Novel Benzimidazole Derivative

AbstractElectrochemical analysis of 2‐(2‐methylbenzyl)‐4(7)‐phenyl‐1‐H‐benzo[d]imidazole (MPB), a new benzimidazole derivative with tyrosinase inhibitory effect and antioxidant activity, was performed in this study. The electro‐oxidation behavior of MPB was investigated by cyclic voltammetry (CV), differential pulse stripping voltammetry (DPSV), and square wave voltammetry (SWV) on glassy carbon electrode. The oxidation process of MPB showed an irreversible behavior. The highest peak current was obtained in 0.5 M H2SO4 containing 10 % methanol and used as the supporting electrolyte. As a result of the calibration study, two linear responses in the range of 0.06–1.00 μM and 2.00–100 μM were obtained with a detection limit of 10.4 nM by DPSV. Linearity for SWV was between 0.1 and 10.0 μM with a detection limit of 29.3 nM. Precision of the methods was obtained as relative standard deviation (RSD) and was below 2.0 %. Developed methods were applied for the recovery of MPB from spiked serum samples. Accordingly, recoveries of 100.39 % for DPSV and 100.07 % for SWV were obtained with RSD below 0.48 %. MPB was stable for at least 2 weeks as a result of retaining 97 % of the peak current when stored at +4 °C. Finally, the possible responsible group in MPB oxidation was proposed.

Antioxidant and Tyrosinase Inhibitory Activities of Athamanta sicula L. Aqueous Extract

Introduction: Overexpression of tyrosinase in humans causes an increase in melanin production in the skin, which can result in hyperpigmentation consequences such as freckles, melasma, age spots, and melanoma. Free radicals also play a significant role in the increase of the biosynthesis of melanin. Tyrosinase inhibitors capable of inhibiting the biosynthesis of melanin are currently used in various hyperpigmentation and cosmetic agents to control the formation of freckles. Several synthetic tyrosinase inhibitors have been associated with several serious side effects. Also, synthetic antioxidants have many toxicological side effects, including carcinogenicity. There is an increasing interest in the search for natural tyrosinase inhibitors and antioxidant agents. Aims: The objective of this study is to evaluate total polyphenol and flavonoid contents as well as examine the antioxidative and tyrosinase inhibitory effects of A. sicula L. aqueous extract. Methods: Antioxidant activities were evaluated using superoxide radical scavenging and reducing power methods. Moreover, a tyrosinase inhibitory assay was used to determine anti-hyperpigmentation. Results: The results showed that this extract was rich in total polyphenols (58.01 ± 1.18 micrograms of gallic acid equivalents per milligrams of extract) and flavonoids (17.91 ± 1.81 micrograms quercetin equivalents per milligram of extract). A. sicula L. aqueous extract was capable of scavenging free radicals (IC50 = 11.87 ± 0.13 μg/mL) and acting as a strong reducing agent (A 0.5= 6.37 ± 0.42 μg/mL). A. sicula L. had a potent tyrosinase inhibitory potential (IC50= 12.63 ± 1.15 μg/mL), which was higher compared to kojic acid used as a standard (IC50= 25,23 ± 0,78 μg/mL, p <0.001). Conclusion: These results support that A. sicula L. could be a new source of antioxidant and cosmetic use. Further studies focusing on the isolation and characterization of active principles of antioxidant and tyrosinase inhibitory activities are needed.

Whitening Activity of Acteoside from Stachys sieboldii Fermented with Hericium erinaceus Mycelia on Melanocytes

Skin whitening has recently renewed attention on Chinese herbal medicines with whitening activity for esthetic applications. Stachys sieboldii has been used as herbal medicine since ancient times and has the potential for development as a cosmetic material because of its astringent effect. In this study, with an aim to develop new functional materials with whitening effects, S. sieboldii water extracts were fermented with different mushroom mycelia. Fermented with Hericium erinaceus mycelia showed the strongest tyrosinase inhibition effect and the lowest melanin content. Thus, H. erinaceus mycelia, the most potent inhibitor of melanogenesis, was used for large-scale fermentation and fractionated. The ethyl acetate fraction, which had the strongest whitening activity, was separated and purified using HPLC. Finally, the single compound was isolated and identified as acteoside, which has promising whitening activity. Acteoside inhibited melanin synthesis and intracellular tyrosinase activity in a dose-dependent manner. The effects of acteoside on the expression of TYR, TRP-1, TRP-2, and MITF were analyzed using Western blot analysis, which showed that acteoside reduced the protein in a dose-dependent manner. Our findings reveal the potential applicability of S. sieboldii extract fermented with H. erinaceus mycelia and its useful component, which is an acteosid, for skin lightening and the treatment of pigmentation.

Chemical Characterization of Different Extracts from Artemisia annua and Their Antioxidant, Enzyme Inhibitory and Anti-Inflammatory Properties.

Artemisia annua L. (Asteraceae Family) is an important plant in Asia that has been used for treating different diseases, including fever due to malaria, wounds, tubercolisis, scabues, pain, convulsions, diabetes, and inflammation. In this study we aimed to evaluate the effects of different polarity extracts (hexane, dichloromethane, ethyl acetate, ethanol, ethanol/water (70 %) and water) from A. annua against the burden of inflammation and oxidative stress occurring in colon tissue exposed to LPS. In parallel, chemical composition, antiradical, and enzyme inhibition effects against α-amylase, α-glucosidase, tyrosinase, and cholinesterases were evaluated. The water extract contained the highest content of the total phenolic with 34.59 mg gallic acid equivalent (GAE)/g extract, while the hexane had the highest content of the total flavonoid (20.06 mg rutin equivalent (RE)/g extract). In antioxidant assays, the polar extracts (ethanol, ethanol/water and water) exhibited stronger radical scavenging and reducing power abilities when compared to non-polar extracts. The hexane extract showed the best AChE, tyrosinase and glucosidase inhibitory effects. All extracts revealed effective anti-inflammatory agents, as demonstrated by the blunting effects on COX-2 and TNFα gene expression. These effects seemed to be not related to the only phenolic content. However, it is worthy of interest to highlight how the higher potency against LPS-induced gene expression was shown by the water extract ; thus suggesting a potential phytotherapy application in the management of clinical symptoms related to inflammatory colon diseases, although future in vivo studies are needed to confirm such in vitro and ex vivo observations.

Synthesis and Evaluation of Some Sulfonamide-Substituted of 1,3,5-Triphenyl Pyrazoline Derivatives as Tyrosinase Enzyme Inhibitors

Pyrazoline is well-known as heterocycles compound that can exhibit many biological effects. In this work, we synthesized a series of sulfonamide-substituted 1,3,5-triphenyl pyrazoline compounds as a promising tyrosinase inhibitor agent. These compounds prepared by multicomponent reaction of corresponding aldehyde, ketone, and hydrazine using seal-vessel reactor. Pyrazolines compound were tested for their tyrosinase inhibitor activity through in vitro assay. The test result found that compound 4c, 4d, and 4e possessed better tyrosinase inhibitory activity compared to the reference drug, kojic acid. Compound 4c exhibited the strongest tyrosinase inhibitory effect with an IC50 value of 30.14 µM. The results suggested that hydroxyl and methoxy substituent at para position are preferable. Furthermore, molecular docking studies result match the pattern of in vitro assay where the compound will provide a stronger binding interaction and lower binding free energies.  

Secondary Metabolites from the Cultures of Medicinal Mushroom Vanderbylia robiniophila and Their Tyrosinase Inhibitory Activities.

Vanderbylia robiniophila (Huaier in Chinese) has been used as a traditional herbal medicine in China for over 1600 years. However, the secondary metabolites of V. robiniophila have not been systematically examined. Corresponding chemical investigation in this study led to the discovery of two new compounds, (22E, 24R)-6β, 7α-dimethoxyergosta-8(14), 22-diene-3β, 5α-diol (1) and vanderbyliolide A (8), along with eight known ones (2-7, 9-10). Their structures were determined by extensive spectroscopic analyses and electronic circular dichroism (ECD) calculations. The tyrosinase inhibitory activity of all isolated compounds was evaluated, and compound 10 showed a potential tyrosinase inhibitory effect with an IC50 value of 60.47 ± 2.63 μM. Kinetic studies of the inhibition reactions suggested that 10 provides the inhibitory ability on tyrosinase in an uncompetitive way.

Triterpenoids and Indole Alkaloids from the Aerial Parts of Asystasia gangetica (L.) T. Anderson

Asystasia gangetica (L.) T. Anderson is an edible vegetable, cultivated in Vietnam. This plant was reported to contain a diverse chemical composition including megastimans, flavonoids, iridoids, and phenylpropanoid glycosides. It also exhibited many interesting biological activities such as antibacterial, antifungal, antihypertensive, anti-asthmatic, analgesic, anti-inflammatory, tyrosinase inhibitory, antioxidant, and antidiabetic effects. However, so far, the studies on this species in Vietnam are relatively few. In this study, six compounds including lutein (1), verbascoside (2), indole-3-carboxylic acid (3), 3α,24-dihydroxy-olean-12-en-28-oic acid (4), ursolic acid (5), and pomolic acid (6) were isolated from the ethyl acetate fraction of the aerial parts of A. gangetica. Their structures were identified based on the NMR and MS spectroscopic data and comparison with those in the literature. Four compounds (3-6) have been isolated from this plant for the first time.

Review: Potensi Resin Kemenyan (Styrax benzoin) dan Senyawa Aktifnya Dalam Pengobatan Penyakit

Studies on drug discovery from natural ingredients are important to determine the pharmacological effects of the compound’s content so that it can be used to treat diseases. Kemenyan (Styrax benzoin) resin has been widely used by the local community for various purposes, including medicine. This review article aims to provide a comprehensive view of the potency of Kemenyan resin and its active compounds so that they could be used and developed to treat diseases in the future. The method used was based on searching for scientific literature in national and international journals. The results showed that the Kemenyan resin contains active compounds, including cinnamic acid, benzoic acid, benzaldehyde, benzyl benzoate, vanillin, styrene, styracin, coniferyl benzoate, benziresinol resin, resinotannol, sterols, phthalic acid, and sumaresorcinol. These compounds are known to have various pharmacological effects, including antibacterial, anesthetic, anti-inflammatory, antispasmodic, antimutagenic, fungicidal, herbicidal, tyrosinase inhibitory, and LDL synthesis inhibitory effects. Based on these studies, it can be concluded that the Kemenyan resin has great potential for the treatment of various diseases.

Homobimetallic Au(I)-Au(I) and Heterotrimetallic Au(I)-Fe(II)-Au(I) Complexes with Dialkyldithiophosphates and Phosphine Ligands: Structural Characterization, DFT Analysis, and Tyrosinase Inhibitory and Biological Effects.

The role of bridging and terminal ligand electronic and steric properties on the structure and antiproliferative activity of two-coordinated gold(I) complexes was investigated on seven novel binuclear and trinuclear gold(I) complexes synthesized by the reaction of either Au2(dppm)Cl2, Au2(dppe)Cl2, or Au2(dppf)Cl2 with potassium diisopropyldithiophosphate, K[(S-OiPr)2], potassium dicyclohexyldithiophosphate, K[(S-OCy)2], or sodium bis(methimazolyl)borate, Na(S-Mt)2, which afforded air-stable gold(I) complexes. In 1-7, the gold(I) centers adopt a two-coordinated linear geometry and are structurally similar. However, their structural features and antiproliferative properties highly depend upon subtle ligand substituent changes. All complexes were validated by 1H, 13C{1H}, 31P NMR, and IR spectroscopy. The solid-state structures of 1, 2, 3, 6, and 7 were confirmed using single-crystal X-ray diffraction. A density functional theory geometry optimization calculation was used to extract further structural and electronic information. To investigate the possible cytotoxicities of 2, 3, and 7, in vitro cellular tests were carried out on the human cancerous breast cell line MCF-7. 2 and 7 show promising cytotoxicity.

Glutamate, Humic Acids and Their Combination Modulate the Phenolic Profile, Antioxidant Traits, and Enzyme-Inhibition Properties in Lettuce.

Lettuce (Lactuca sativa L., Asteraceae) is a popular vegetable leafy crop playing a relevant role in human nutrition. Nowadays, novel strategies are required to sustainably support plant growth and elicit the biosynthesis of bioactive molecules with functional roles in crops including lettuce. In this work, the polyphenolic profile of lettuce treated with glutamic acid (GA), humic acid (HA), and their combination (GA + HA) was investigated using an untargeted metabolomics phenolic profiling approach based on high-resolution mass spectrometry. Both aerial and root organ parts were considered, and a broad and diverse phenolic profile could be highlighted. The phenolic profile included flavonoids (anthocyanins, flavones, flavanols, and flavonols), phenolic acids (both hydroxycinnamics and hydroxybenzoics), low molecular weight phenolics (tyrosol equivalents), lignans and stilbenes. Overall, GA and HA treatments significantly modulated the biosynthesis of flavanols, lignans, low molecular weight phenolics, phenolic acids, and stilbene. Thereafter, antioxidant capacity was evaluated in vitro with 2,2-diphenyln-1-picrylhydrazyl (DPPH), 2,2'-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), and cupric ion reducing antioxidant capacity (CUPRAC) assays. In addition, this study examined the inhibitory properties of enzymes, including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), tyrosinase, alpha-amylase, and alpha-glucosidase. Compared to individual treatments, the combination of GA + HA showed stronger antioxidant abilities in free radical scavenging and reducing power assays in root samples. Moreover, this combination positively influenced the inhibitory effects of root samples on AChE and BChE and the tyrosinase inhibitory effect of leaf samples. Concerning Pearson's correlations, antioxidant and enzyme inhibition activities were related to phenolic compounds, and lignans in particular correlated with radical scavenging activities. Overall, the tested elicitors could offer promising insights for enhancing the functional properties of lettuce in agricultural treatments.