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1.
Chem Pharm Bull (Tokyo) ; 67(9): 985-991, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31270295

RESUMO

Chemically stable ester derivatives of taxifolin have become a focus of interest for their role in the satisfactory effects on human health. Accordingly, the aim of this study was to evaluate the physical and chemical stability of different formulations containing 0.02% taxifolin tetra-octanoate, which was proved to possess higher inhibitory effect on tyrosinase activity compared with taxifolin in a cell-free system. In the studies of physical stability, a Brookfield viscometer was used to determine rheological behavior of formulations containing taxifolin tetra-octanoate, and a portable pH meter was used to determine pH change. Moreover, chemical stability was determined by HPLC with UV detection. Formulations were evaluated for 12 weeks stored at 25 and 40°C. Results showed that storage time had no significant influence on viscosity of the formulations containing taxifolin tetra-octanoate, and pH value was relatively stable, which was within the limits of normal skin pH range. In the chemical stability studies, taxifolin tetra-octanoate in the essence formulation was most unstable at 40°C with about 81% degradation in 12 weeks of storage, however, the percentage of remaining taxifolin tetra-octanoate in cream formulation stored for 12 weeks at 25°C was the highest, about 93%. The results in this study may contribute to the development of more stable formulations containing taxifolin tetra-octanoate.


Assuntos
Caprilatos/farmacologia , Inibidores Enzimáticos/farmacologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Quercetina/análogos & derivados , Caprilatos/síntese química , Caprilatos/química , Cromatografia Líquida de Alta Pressão , Composição de Medicamentos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Humanos , Concentração de Íons de Hidrogênio , Estrutura Molecular , Monofenol Mono-Oxigenase/metabolismo , Quercetina/síntese química , Quercetina/química , Quercetina/farmacologia , Relação Estrutura-Atividade , Viscosidade
2.
Planta Med ; 85(11-12): 941-946, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31163460

RESUMO

Targeted isolation based on a combination of NMR and HPLC-PDA-MS of a dichloromethane extract of Thymus vulgaris Varico 3 aerial parts afforded one new p-cymene dimer, 6,3',4'-trihydroxy-5,5'-diisopropyl-2,2'-dimethylbiphenyl (1: ), together with two known p-cymene derivatives (2: and 3: ), as well as five known compounds, namely, thymol (4: ), oleanolic acid (5: ), ursolic acid (6: ), cirsimaritin (7: ), and xanthomicrol (8: ). The structural elucidation of all compounds was performed by spectroscopic analyses, including 1D and 2D NMR, and HRESIMS experiments. The biphenyls were assayed for their inhibitory activity on tyrosinase. Compounds 2: and 3: showed negligible activity on tyrosinase, while compound 1: effectively inhibited the enzyme with 35% (± 0.3) inhibitory activity, higher than the inhibition of the reference compound kojic acid (18.6 ± 0.02).


Assuntos
Cromatografia Gasosa-Espectrometria de Massas/métodos , Espectroscopia de Ressonância Magnética/métodos , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monoterpenos/isolamento & purificação , Extratos Vegetais/química , Thymus (Planta)/química , Flavonas/farmacologia , Monoterpenos/farmacologia , Ácido Oleanólico/farmacologia , Timol/farmacologia , Triterpenos/farmacologia
3.
Food Chem ; 297: 124910, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31253292

RESUMO

Polyphenols can inhibit the enzymatic browning in food, but their indistinct synergistic effect and conformational change have limited their applications. In this paper, the mixture of quercetin, cinnamic acid and ferulic acid (Group 11, KI = 0.239 mM) possessed a higher inhibition ability than quercetin (KI = 0.361 mM), which could promote the spontaneous binding process. The final Group 11-tyrosinase complex is more stable, and the hydrophobic effect is the major driving force during the binding process. Moreover, there is not a direct relationship between the destruction of secondary structures and catalytic activity of tyrosinase. The interaction between ferulic acid and tyrosinase could destroy the secondary structures of enzyme but it had little impact on the tyrosinase activity. Molecular docking suggested that three polyphenols from Group 11 have synergistic effect on tyrosinase. This study provides new perspectives about the development of tyrosinase inhibitors in food products.


Assuntos
Inibidores Enzimáticos/química , Monofenol Mono-Oxigenase/antagonistas & inibidores , Polifenóis/química , Sítios de Ligação , Cinamatos/química , Cinamatos/metabolismo , Ácidos Cumáricos/química , Ácidos Cumáricos/metabolismo , Inibidores Enzimáticos/metabolismo , Cinética , Simulação de Acoplamento Molecular , Monofenol Mono-Oxigenase/metabolismo , Estrutura Secundária de Proteína , Termodinâmica
4.
Food Chem Toxicol ; 131: 110563, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31199992

RESUMO

Apple pomace (AP) utilised for analysis of triterpenic acids (TTAs) using HPLC-MS/MS. The methanol, ethanol and ethyl acetate extracts showed high phenolic content with significant antioxidant activity compared to chloroform and n-hexane. AP TTAs; ursolic acid, betulinic acid and maslinic acid showed potent antioxidant and enzyme inhibitory effects. The IC50 values were 13.2-30.8 µg/mL (tyrosinase), 19.6-42.5 µg/mL (xanthine oxidase) and 16.6-38.6 µg/mL (urease) for AP extracts and 8.4-25.8 µg/mL (tyrosinase), 12.6-30.2 µg/mL (xanthine oxidase) and 10.1-28.6 µg/mL (urease) for TTAs, compared to the positive controls; kojic acid (10.4 ±â€¯0.06 µg/mL), allopurinol (9.6 ±â€¯0.04 µg/mL) and thiourea (8.9 ±â€¯0.02 µg/mL) towards respective enzymes. UA showed a competitive type of inhibition for tyrosinase, while BA showed a noncompetitive type of inhibition towards xanthine oxidase. In addition, the AP extracts and TTAs exerted significant cytotoxic effects towards the proliferation of cancer cell lines. AP methanol extract (IC50 of 38.5 ±â€¯4.1, 47.1 ±â€¯3.5, 70.6 ±â€¯2.3, and 50.5 ±â€¯3.9 µg/mL) and ursolic acid (IC50 of 6.5 ±â€¯0.7, 15.5 ±â€¯1.4, 20.8 ±â€¯1.3, and 5.6 ±â€¯0.8 µg/mL) showed prominent anticancer activity on Hela, Skov-3, Caski, and NCL cancer cell lines, respectively. Thus, this study shows that the AP & TTAs could be utilized for functional food development and as a potent antioxidant, anticancer, skin whitening, and anti-urolithic agents.


Assuntos
Antineoplásicos/farmacologia , Inibidores Enzimáticos/farmacologia , Depuradores de Radicais Livres/farmacologia , Frutas/química , Malus/química , Triterpenos/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Cães , Ensaios Enzimáticos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/isolamento & purificação , Humanos , Células Madin Darby de Rim Canino , Monofenol Mono-Oxigenase/antagonistas & inibidores , Extratos Vegetais/análise , Extratos Vegetais/química , Extração em Fase Sólida , Triterpenos/química , Triterpenos/isolamento & purificação , Urease/antagonistas & inibidores , Xantina Oxidase/antagonistas & inibidores
5.
Eur J Med Chem ; 178: 380-389, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31202126

RESUMO

The development of Tyrosinase inhibitors (TYRIs) could represent an efficacious strategy for pharmacological intervention on skin pathologies related to aberrant production of melanin. Based on in silico studies we designed and tested a library of twenty-four compounds bearing the 4-(4-fluorobenzyl)piperazin-1-yl]-fragment. As result, we identified several compounds with excellent inhibit effects at low micromolar concentration against TYR from Agaricus bisporus (TyM). Among them, compound 25 (IC50 = 0.96 µM) proved to be ∼20-fold more potent than the reference compound kojic acid (IC50 = 17.76 µM) having wide applications in the cosmetics and pharmaceutical industries. The mode of interaction of active inhibitor 25 was deciphered by means of crystallography as well as molecular docking and these results were consistent with kinetic experiments. Moreover, the identified compound 25 exhibited no considerable cytotoxicity and showed anti-melanogenic effects on B16F10 melanoma cells. Therefore, a combination of computational and biochemical approaches could represent a rational guidelines for further structural modification of this class of compounds as future anti-melanogenic agents.


Assuntos
Antineoplásicos/farmacologia , Desenho de Drogas , Inibidores Enzimáticos/farmacologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Agaricus/química , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Humanos , Modelos Moleculares , Estrutura Molecular , Monofenol Mono-Oxigenase/metabolismo , Relação Estrutura-Atividade
6.
J Sci Food Agric ; 99(13): 6001-6010, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31225640

RESUMO

BACKGROUND: In this study, we aimed to evaluate the influence of different extraction procedures [decoction, homogenizer-assisted extraction (HAE), infusion, maceration, Soxhlet and ultrasound-assisted extraction (UAE)] on the chemical profiling and biological properties of methanol and water extracts of Pulicaria dysenterica (L.) Bernh. The chemical profiles of the extracts were evaluated by high-performance liquid chromatography coupled to electrospray ionization and time-of-flight mass spectrometry (HPLC-ESI-TOF-MS). The antioxidant properties and enzymes (lipase, α-amylase, α-glucosidase, tyrosinase and cholinesterases) inhibitory potential of the extracts were evaluated. RESULTS: The chemical profiles were dependent on the type of extraction methods as well as on the type of solvent. The methanolic extracts showed higher levels of total phenolic, flavonoid, and phenolic acid content, while the highest total flavonol content was observed in the HAE-water extract. Forty different compounds were identified from P. dysenterica. In relation to the potential in vitro anti-diabetic effects, the highest activity against the studied key enzymes was observed for the macerated extract (α-amylase: 0.58 ± 0.03 and α- glucosidase: 1.65 ± 0.03 mmol ACAE g-1 ). The HAE-methanol extract was the most potent inhibitor of cholisterases, whereas the highest activities against tyrosinase were observed for UAE-methanol extract, followed by macerated and Soxhlet. The inhibitory activity of the studied extracts against lipase were in the order: soxhlet > macerated> HAE-methanol > UAE-methanol. CONCLUSION: This study has established scientific baseline data on the therapeutic properties of P. dysentrica, thereby advocating the need for further investigations in an endeavour to develop novel pharmaceuticals from this plant. © 2019 Society of Chemical Industry.


Assuntos
Extratos Vegetais/química , Pulicaria/química , Antioxidantes/química , Antioxidantes/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Flavonoides/química , Flavonoides/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/química , Análise Multivariada , Fenóis/química , Fenóis/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Espectrometria de Massas por Ionização por Electrospray , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/química , alfa-Glucosidases/química
7.
Mini Rev Med Chem ; 19(10): 796-808, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31244414

RESUMO

Cutaneous pigmentation plays critical role in determining the color of skin along with photo protection of skin from dreadful effects of ultraviolet radiations. Conversely, abnormal accumulation of melanin is responsible for hyper pigmentary disorders such as melasma, senile lentigines and freckles. Because of the visible nature of dermatologic diseases, they have a considerable psychosomatic effect on affected patients. Tyrosinase inhibitors are molecules that interrelate in some way with the enzyme to prevent it from working in the normal manner. Past many decades witnessed the quest for the development of natural tyrosinase inhibitors due to imperative role played by tyrosinase in the process of melanogenesis and fungi or fruit enzymatic browning. Mechanism of pigmentation is characterized by the intact process of the synthesis of specialized black pigment within melanosomes. Melanin is synthesized by a cascade of enzymatic and chemical reactions. For this reason, melanin production is mainly controlled by the expression and activation of tyrosinase. In the current article, we discussed tyrosinase inhibitors from the natural sources, which can be an essential constituent of cosmetics products and depigmenting agents for the treatment of hyperpigmentory disorders.


Assuntos
Produtos Biológicos/farmacologia , Inibidores Enzimáticos/farmacologia , Hiperpigmentação/tratamento farmacológico , Melaninas/biossíntese , Monofenol Mono-Oxigenase/antagonistas & inibidores , Fitoterapia , Preparações Clareadoras de Pele/farmacologia , Pigmentação da Pele/efeitos dos fármacos , Animais , Produtos Biológicos/síntese química , Produtos Biológicos/química , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Humanos , Estrutura Molecular , Monofenol Mono-Oxigenase/metabolismo , Preparações Clareadoras de Pele/síntese química , Preparações Clareadoras de Pele/química
8.
J Enzyme Inhib Med Chem ; 34(1): 990-998, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31072148

RESUMO

The novel kojic acid derivatives KAD1 and KAD2 have been demonstrated that they exhibited potent anti-melanogenesis activity in our previous report. In this study, we further study the inhibitory mechanism on mushroom tyrosinase. The inhibitory types of both KADs on diphenolase were classified as mixed type based on the results of the kinetic model. The interaction between KADs and tyrosinase was illustrated by fluorescence quenching, molecular docking and copper chelate activity. The KADs were also evaluated with respect to their antioxidant activities by DPPH and ABTS+ assays. The results showed that KADs have more potent antioxidant activities than kojic acid. Our study could provide new ideas for the development of new anti-tyrosinase and antioxidant agents.


Assuntos
Antioxidantes/farmacologia , Inibidores Enzimáticos/farmacologia , Simulação de Acoplamento Molecular , Monofenol Mono-Oxigenase/antagonistas & inibidores , Pironas/farmacologia , Agaricales/enzimologia , Antioxidantes/química , Benzotiazóis/antagonistas & inibidores , Compostos de Bifenilo/antagonistas & inibidores , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Cinética , Monofenol Mono-Oxigenase/metabolismo , Picratos/antagonistas & inibidores , Pironas/química , Espectrometria de Fluorescência , Relação Estrutura-Atividade , Ácidos Sulfônicos/antagonistas & inibidores
9.
J Enzyme Inhib Med Chem ; 34(1): 927-936, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31039625

RESUMO

Skin ageing results from enhanced activation of intracellular enzymes such as collagenases, elastases and tyrosinase, stimulated by intrinsic ageing and photoageing factors. Recently, caffeine-based cosmetics are introduced that demonstrates to slow down skin photoageing process. However, no attempts have been done so for to understand caffeine functional inhibitory activity against photoageing related enzymes. Hence, this study established the caffeine molecular interaction and inhibition activity profiles against respective enzymes using in silico and in vitro methods, respectively. Results from in silico study indicates that caffeine has comparatively good affinity with collagenase (-4.6 kcal/mol), elastase (-3.36 kcal/mol) and tyrosinase (-2.86 kcal/mol) and formed the stable protein-ligand complex as validated by molecular dynamics simulation (protein-ligand contacts, RMSD, RMSF and secondary structure changes analysis). Moreover, in vitro data showed that caffeine (1000 µg/mL) has statistically significant maximum inhibition activity of 41.86, 36.44 and 13.72% for collagenase, elastase and tyrosinase, respectively.


Assuntos
Cafeína/farmacologia , Colagenases/metabolismo , Simulação por Computador , Inibidores Enzimáticos/farmacologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Elastase Pancreática/antagonistas & inibidores , Agaricus/enzimologia , Animais , Cafeína/química , Clostridium histolyticum/enzimologia , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Técnicas In Vitro , Ligantes , Simulação de Dinâmica Molecular , Monofenol Mono-Oxigenase/metabolismo , Pâncreas/enzimologia , Elastase Pancreática/metabolismo , Relação Estrutura-Atividade , Suínos
10.
Eur J Med Chem ; 175: 162-171, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31082763

RESUMO

We have designed novel tropinone-thiazole derivatives that showed high antiproliferative activity against a variety of cancer cell lines via caspase 3/7 activation mechanism. Among the derivatives, compounds 3b-3h were found to exhibit high activity against human leukemia (MV4-11), human lung carcinoma (A549), human breast carcinoma (MCF-7), and skin melanoma (B16-F10) cancer cell lines, with IC50 values of 5.43-11.06 µM. The lead compound 3g increases caspase 3/7 activity in A549 cells 25 times more than the control, and 2 times more than reference drug camptothecin. We have also found that tropinone-thiazole derivatives exhibit high tyrosinase inhibitory activity. The lead compounds 3g and 3h showed tyrosinase inhibition effect, with IC50 values 3.22 and 3.51 µM, respectively. These inhibitory activities are 22 times higher than the activity of kojic acid (IC50 72.27 µM) and 120 times higher than activity of ascorbic acid (IC50 386.5 µM). For compounds 3g and 3h, the experimentally determined lipophilicity correlates very well with their enzymatic activities. These data suggest that presented compounds could constitute lead anticancer drug candidates.


Assuntos
Caspase 3/metabolismo , Caspase 7/farmacologia , Proliferação de Células/efeitos dos fármacos , Descoberta de Drogas , Ativadores de Enzimas/farmacologia , Inibidores Enzimáticos/farmacologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Tiazóis/química , Tropanos/química , Células 3T3 , Animais , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Caspase 7/química , Linhagem Celular Tumoral , Cromatografia Líquida/métodos , Ensaios de Seleção de Medicamentos Antitumorais , Ativadores de Enzimas/química , Inibidores Enzimáticos/química , Humanos , Concentração Inibidora 50 , Camundongos , Camundongos Endogâmicos BALB C , Espectroscopia de Prótons por Ressonância Magnética , Espectrometria de Massas por Ionização por Electrospray/métodos , Relação Estrutura-Atividade
11.
Chem Biodivers ; 16(7): e1900167, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31145516

RESUMO

A dozen of phosphonic and phosphinic acid derivatives containing pyridine moiety were synthesized and its inhibitory activity toward mushroom tyrosinase was investigated. Moreover, molecular docking of these compounds to the active site of the enzyme was performed. All the compounds (1-10) demonstrated the inhibitory effect with the IC50 and inhibition constants ranging millimolar concentrations. The obtained results indicate that the compounds show different types of inhibition (competitive, noncompetitive, mixed), but all of them are reversible inhibitors. The obtained outcomes allowed to make the structure-activity relationship (SAR) analysis. Compound 4 ([(benzylamino)(pyridin-2-yl)methyl]phenylphosphinic acid) revealed the lowest IC50 value of 0.3 mm and inhibitory constant of Ki 0.076 mm, with noncompetitive type and reversible mechanism of inhibition. According to SAR analysis, introducing bulky phenyl moieties to phosphonic and amino groups plays an important role in the inhibitory potency on activity of mushroom tyrosinase and could be useful in design and development of a new class of potent organophosphorus inhibitors of tyrosinase. Combined results of molecular docking and SAR analysis can be helpful in designing novel tyrosinase inhibitors of desired properties. They may have broad application in food industry and cosmetology.


Assuntos
Inibidores Enzimáticos/farmacologia , Simulação de Acoplamento Molecular , Monofenol Mono-Oxigenase/antagonistas & inibidores , Ácidos Fosfínicos/farmacologia , Ácidos Fosforosos/farmacologia , Agaricus/enzimologia , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Cinética , Estrutura Molecular , Monofenol Mono-Oxigenase/metabolismo , Ácidos Fosfínicos/química , Ácidos Fosfínicos/isolamento & purificação , Ácidos Fosforosos/química , Ácidos Fosforosos/isolamento & purificação , Relação Estrutura-Atividade
13.
J Enzyme Inhib Med Chem ; 34(1): 853-862, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31010356

RESUMO

The ethyl ether extract of agarwood from an Aquilaria plant afforded six new sesquiterpenoids, Agarozizanol A - F (1-6), together with four known sesquiterpenoids and six known 2-(2-phenylethyl)chromones. Their structures were elucidated via detailed spectroscopic analysis, X-ray diffraction, and comparisons with the published data. All the isolates were evaluated for the α-glucosidase and tyrosinase inhibitory activities in vitro. Compounds 5, 7, 8, and 10 showed significant inhibition of α-glucosidase with IC50 values ranging between 112.3 ± 4.5 and 524.5 ± 2.7 µM (acarbose, 743. 4 ± 3.3 µM). Compounds 13 and 14 exhibited tyrosinase inhibitory effect with IC50 values of 89.0 ± 1.7 and 51.5 ± 0.6 µM, respectively (kojic acid, 46.1 ± 1.3). In the kinetic studies, compounds 5 and 14 were found to be uncompetitive inhibitors for α-glucosidase and mixed type inhibitors for tyrosinase, respectively. Furthermore, molecular docking simulations revealed the binding sites and interactions of the most active compounds with α-glucosidase and tyrosinase.


Assuntos
Cromonas/isolamento & purificação , Cromonas/farmacologia , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/farmacologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Thymelaeaceae/química , Madeira/química , Cromonas/química , Inibidores Enzimáticos/química , Inibidores de Glicosídeo Hidrolases/química , Concentração Inibidora 50 , Cinética , Simulação de Acoplamento Molecular , Estrutura Molecular , Sesquiterpenos/química , Análise Espectral/métodos
14.
Int J Med Mushrooms ; 21(3): 275-289, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31002611

RESUMO

Previous studies showed that some mushrooms are highly efficient in inhibiting acetylcholinesterase and tyrosinase, the increased activity of which can trigger the development of Alzheimer and Parkinson diseases. Starting from the fact that free radicals at high concentrations could cause neurodegenerative disorders as well as great interest in new, natural antineurodegenerative drugs, the goal of this study was to determine the in vitro antioxidative and neuroprotective potentials of various Pleurotus ostreatus and Laetiporus sulphureus extracts. L. sulphureus was a better antioxidative agent; it showed higher reducing power, was a more efficient scavenger of DPPH and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) radicals, and was an Fe3+ reducer. The most efficient acetylcholinesterase inhibitor was hot water extract of P. ostreatus fruiting body, which was slightly weaker than the commercial preparation, galantamine. However, in comparison with α-kojic acid, tested extracts were weaker tyrosinase inhibitors. Considering that tested extracts were rich in phenols and that their amounts were in positive correlation with the extent of radical neutralization and acetylcholinesterase and tyrosinase inhibition, it is assumed that these compounds are the potential carriers of the neuroprotective activities. Owing to the significant antioxidative and antineurodegenerative capacity of these species, they can be suggested as novel nutraceuticals and pharmaceuticals.


Assuntos
Antioxidantes/farmacologia , Produtos Biológicos/farmacologia , Descoberta de Drogas , Pleurotus/química , Doença de Alzheimer/tratamento farmacológico , Produtos Biológicos/química , Inibidores da Colinesterase/farmacologia , Carpóforos/química , Humanos , Monofenol Mono-Oxigenase/antagonistas & inibidores , Micélio/química , Doença de Parkinson/tratamento farmacológico
15.
Phytochemistry ; 163: 33-37, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30986688

RESUMO

An undescribed isoprenylated flavonol racemate, nigranol C, with an unprecedented 7/6/6 ring system, was isolated from the twigs of Morus nigra L. The structure was assigned through a comprehensive analysis of HRMS, IR, and NMR data. Chiral separation of nigranol C was successfully carried out to yield a pair of enantiomers, nigranol C-a and nigranol C-b, whose absolute configurations were determined by ECD calculation. A plausible biogenetic pathway for nigranol C was proposed. A previously isolated sanggenon-type flavonone racemate, nigragenon E, was also well resolved by chiral HPLC to offer another pair of enantiomers, nigragenon E-a and nigragenon E-b, whose stereo configurations were determined by ECD data. All of the isolated compounds showed prominent α-glucosidase inhibitory activities with IC50 values ranging from 9.79 to 30.21 µM, while only the sanggenon-type flavonones exhibited tyrosinase inhibitory effects comparable to that of the positive control, kojic acid, the IC50 value of which was 27.14 µM. In addition, it was found that the stereo configurations of these compounds seemed to play a negligible role in their inhibitory activities towards the two enzymes.


Assuntos
Inibidores Enzimáticos/farmacologia , Flavonoides/farmacologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Morus/química , alfa-Glucosidases/metabolismo , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Flavonoides/química , Flavonoides/isolamento & purificação , Conformação Molecular , Monofenol Mono-Oxigenase/metabolismo , Relação Estrutura-Atividade
16.
Chem Biodivers ; 16(4): e1800648, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30874370

RESUMO

The chemical composition of the essential oil (LEO) and its volatile fractions (V1 -V10 ) collected during the hydrodistillation process every 15 min from the fresh leaves of I. viscosa (L.), growing in Tunisia, were analyzed by GC-FID and GC/MS. Eighty-two compounds, representing 90.9-99.4 % of the total samples, were identified. The crude essential oil (LEO) and its fractions (V1 -V10 ) were characterized by the presence of a high amount of oxygenated sesquiterpenes (82.7-95.8 %). Isocostic acid (1) was found to be the most abundant component (37.4-83.9 %) and was isolated from the same essential oil over silica gel column chromatography and identified by spectroscopic methods (1 H, 13 C, DEPT 135 NMR and EI-MS) and by comparison with literature data. Furthermore, the fresh leaves essential oil (LEO), its volatile fractions (V1 -V10 ) as well as compound 1 were screened for their antibacterial, antityrosinase, anticholinesterase and anti-5-lipoxygenase activities. It was found that the isolated compound 1 exhibited an interesting antibacterial activity against Staphylococcus aureus ATCC 25923 (MIC=32 µg/mL) and Enterococcus faecalis ATCC 29212 (MIC=32 µg/mL) and the highest antityrosinase activity (IC50 =13.82±0.87 µg/mL). Compound 1 was also found to be able to strongly inhibit 5-lipoxygenase with an IC50 value of 59.21±0.85 µg/mL. The bioactivity and drug likeness scores of compound 1 were calculated using Molinspiration software and interpreted, and the structure-activity relationship (SAR) was discussed with the help of molecular docking analysis.


Assuntos
Antibacterianos/farmacologia , Inibidores Enzimáticos/farmacologia , Inula/química , Simulação de Acoplamento Molecular , Naftalenos/farmacologia , Óleos Voláteis/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Araquidonato 5-Lipoxigenase/metabolismo , Relação Dose-Resposta a Droga , Enterococcus faecalis/efeitos dos fármacos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/metabolismo , Naftalenos/química , Naftalenos/isolamento & purificação , Óleos Voláteis/síntese química , Óleos Voláteis/química , Folhas de Planta/química , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-Atividade , Tunísia
17.
Int J Biol Macromol ; 131: 309-314, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30872058

RESUMO

The present paper aimed to obtain the polysaccharides with potent tyrosinase inhibitory activity from chestnut kernel. The ultrasound extracted polysaccharide fractions 1-1 (UEP1-1) and UEP2-1 were obtained by successive ultrasound-assisted-extraction, DEAE-52 and Sephadex G-100 chromatography. The Fourier transform infrared spectrum revealed that both UEP1-1 and UEP2-1 had the characteristic absorption peaks of polysaccharides. The degree of esterification of UEP1-1 (52.4%) and UEP2-1 (49.0%) was higher than that of the crude UEP (33.0%), indicating that the gel properties of the polysaccharides changed after purification. The x-ray diffraction patterns of UEP1-1 and UEP2-1 suggested that they were semi-crystalline polymers with a degree of crystallinity of 23.9 and 35.8%, respectively. The weight-average molecular weight (Mw) of UEP1-1 and UEP2-1 was 75.4 and 59.9 kDA, respectively. The monosaccharide composition of UEP1-1 and UEP2-1 was glucose, galactose, arabinose, mannose, xylose, rhamnose and fructose with different proportions. UEP1-1 displayed a dose-dependent inhibitory effect on tyrosinase activity, and the inhibition mode was found to be competitive.


Assuntos
Fagaceae/química , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Ativação Enzimática/efeitos dos fármacos , Peso Molecular , Monossacarídeos/química , Polissacarídeos/isolamento & purificação , Análise Espectral
18.
J Enzyme Inhib Med Chem ; 34(1): 279-309, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30734608

RESUMO

Tyrosinase is a multi-copper enzyme which is widely distributed in different organisms and plays an important role in the melanogenesis and enzymatic browning. Therefore, its inhibitors can be attractive in cosmetics and medicinal industries as depigmentation agents and also in food and agriculture industries as antibrowning compounds. For this purpose, many natural, semi-synthetic and synthetic inhibitors have been developed by different screening methods to date. This review has focused on the tyrosinase inhibitors discovered from all sources and biochemically characterised in the last four decades.


Assuntos
Chalcona/farmacologia , Cumarínicos/farmacologia , Inibidores Enzimáticos/farmacologia , Flavonoides/farmacologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Resveratrol/farmacologia , Agaricales/enzimologia , Animais , Chalcona/química , Cumarínicos/química , Inibidores Enzimáticos/química , Flavonoides/química , Humanos , Monofenol Mono-Oxigenase/metabolismo , Resveratrol/química
19.
Molecules ; 24(4)2019 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-30795539

RESUMO

Although melanin production is a key self-defense mechanism against ultraviolet radiation (UVR)-induced skin damage, uneven or excessive deposition of melanin causes hyperpigmentary disorders. Currently available whitening agents are unsatisfactory because of issues with efficacy and safety. To develop more effective depigmenting agents, we performed high-throughput melanin content assay screening using the B16F10 melanoma cell line and identified L-765,314 as a drug that suppressed melanin production in cultured melanocytes in a dose-dependent manner as well as cAMP- or 12-O-tetradecanoylphorbol 13-acetate (TPA)-stimulated melanin production without cytotoxicity. Interestingly, melanogenic gene expression was not altered by L-765,314. Rather, diminished melanin production by L-765,314 appeared to be caused by downregulation of tyrosinase activity via inhibition of protein kinase C (PKC). Because L-765,314 did not show any adverse effect in melanocytes, altogether our data suggest that L-765,314 could be a potential therapeutic candidate for skin hyperpigmentary disorders and further discovery of selective inhibitors targeting PKC might be a promising strategy for the development of depigmenting agents to treat hyperpigmentary disorders.


Assuntos
Clareadores/farmacologia , Inibidores Enzimáticos/farmacologia , Melaninas/antagonistas & inibidores , Monofenol Mono-Oxigenase/antagonistas & inibidores , Prazosina/análogos & derivados , Proteína Quinase C/antagonistas & inibidores , Bibliotecas de Moléculas Pequenas/farmacologia , Animais , Clareadores/química , AMP Cíclico/farmacologia , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Regulação da Expressão Gênica , Ensaios de Triagem em Larga Escala , Melaninas/biossíntese , Melanoma Experimental/genética , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Camundongos , Monofenol Mono-Oxigenase/genética , Monofenol Mono-Oxigenase/metabolismo , Prazosina/química , Prazosina/farmacologia , Proteína Quinase C/genética , Proteína Quinase C/metabolismo , Transdução de Sinais , Bibliotecas de Moléculas Pequenas/química , Acetato de Tetradecanoilforbol/farmacologia , Células Tumorais Cultivadas
20.
Chem Biodivers ; 16(2): e1800483, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30673162

RESUMO

A new caryophyllene, named pulicaryenne A (1), along with four other known caryophyllene derivatives (2, 3, 4 and 5) were isolated from the ethyl acetate extract of aerial parts of Pulicaria vulgaris Gaertn. (Asteraceae). All compounds were isolated for the first time from this species. Compound 2 was identified as a new epimer of a known caryophyllene derivative isolated previously from P. dysenterica. Their structures were established by spectroscopic means including NMR analysis (1D- and 2D-NMR) and ESI-TOF-MS. All compounds were evaluated for their anticholinesterase, antityrosinase and cytotoxic activities against two human cell lines (A549 and HeLa). Results showed that compound 5 exhibited the highest cytotoxic effect against A549 and anticholinesterase activity with IC50 values of 8.50±0.75 and 6.45±0.09 µg/mL, respectively. Furthermore, compound 5 showed also an interesting antityrosinase activity with percent inhibition value of 79.0±2.5 % at 50 µg/mL. The bioactivity and drug likeness scores of the isolated compounds 1-5 were calculated using Molinspiration software and discussed. These results may suggest that the five caryophyllene derivatives endowed with good biological properties, which could be used as bioactive alternatives in pharmaceutical preparations.


Assuntos
Extratos Vegetais/química , Pulicaria/química , Sesquiterpenos/isolamento & purificação , Células A549 , Anti-Inflamatórios não Esteroides , Inibidores da Colinesterase/isolamento & purificação , Inibidores da Colinesterase/farmacologia , Citotoxinas/isolamento & purificação , Citotoxinas/farmacologia , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Células HeLa , Humanos , Estrutura Molecular , Monofenol Mono-Oxigenase/antagonistas & inibidores , Sesquiterpenos/química , Relação Estrutura-Atividade
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