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1.
Int J Mol Sci ; 22(11)2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34073709

RESUMO

Polyphenols are natural organic compounds produced by plants, acting as antioxidants by reacting with ROS. These compounds are widely consumed in daily diet and many studies report several benefits to human health thanks to their bioavailability in humans. However, the digestion process of phenolic compounds is still not completely clear. Moreover, bioavailability is dependent on the metabolic phase of these compounds. The LogP value can be managed as a simplified measure of the lipophilicity of a substance ingested within the human body, which affects resultant absorption. The biopharmaceutical classification system (BCS), a method used to classify drugs intended for gastrointestinal absorption, correlates the solubility and permeability of the drug with both the rate and extent of oral absorption. BCS may be helpful to measure the bioactive constituents of foods, such as polyphenols, in order to understand their nutraceutical potential. There are many literature studies that focus on permeability, absorption, and bioavailability of polyphenols and their resultant metabolic byproducts, but there is still confusion about their respective LogP values and BCS classification. This review will provide an overview of the information regarding 10 dietarypolyphenols (ferulic acid, chlorogenic acid, rutin, quercetin, apigenin, cirsimaritin, daidzein, resveratrol, ellagic acid, and curcumin) and their association with the BCS classification.


Assuntos
Produtos Biológicos/metabolismo , Polifenóis/metabolismo , Animais , Disponibilidade Biológica , Produtos Biológicos/química , Produtos Biológicos/classificação , Produtos Biológicos/farmacocinética , Ácidos Cumáricos , Flavonas , Flavonóis , Humanos , Absorção Intestinal , Isoflavonas , Permeabilidade , Polifenóis/química , Polifenóis/classificação , Polifenóis/farmacocinética , Solubilidade , Estilbenos , Taninos
2.
Drugs Today (Barc) ; 57(5): 347-357, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34061129

RESUMO

Psoriasis is a chronic inflammatory disease that can be triggered by injury, trauma, infection and medications. Genetic and immunologic studies have highlighted the importance of the interleukin (IL)-23/T-helper 17 (Th17) pathway in systemic psoriasis pathogenesis. Main IL-23 is an upstream regulatory cytokine with direct effects on epidermal keratinocytes and other resident skin cells while IL-17, a downstream molecule, can activate inflammatory responses in different cells across a diversity of organs. Disease modification could be achieved with drugs that can slow down the biological processes that cause the persistent inflammation in moderate to severe psoriasis. Early intervention with anti-IL-17 and anti-IL-23 agents in new-onset moderate to severe plaque psoriasis might modify the natural course of the disease. Perhaps we are not simply seeing a pharmacologic and mechanistic effect of new-generation biologics but eventually a disease modification process. In this short report we underline the main available data which supports an important role for IL-17 blockade and address whether these new drugs targeting the IL-23/IL-17 axis could be disease-modifying agents in plaque psoriasis. This type of data gains more relevance in the current pandemic era, where chronic patients undergoing earlier treatment may have better outcomes and consequently avoid constant hospital visits.


Assuntos
Produtos Biológicos , Psoríase , Citocinas , Humanos , Interleucina-17 , Psoríase/tratamento farmacológico
3.
Med Clin North Am ; 105(4): 611-626, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34059241

RESUMO

This is a comprehensive and current guide for the diagnosis, differential diagnosis, treatment, and management of eczematous dermatitis, with a focus on atopic dermatitis, irritant and allergic contact dermatitis, hand dermatitis including recurrent vesicular and hyperkeratotic types, asteatotic dermatitis, and nummular or discoid dermatitis. Diagnostic options highlighted are clinical history, physical examination, and patch testing. Therapeutic options highlighted are moisturizers, topical corticosteroids, topical calcineurin inhibitors, crisaborole, phototherapy, and systemic medications including biologics.


Assuntos
Dermatite Alérgica de Contato/patologia , Dermatite Atópica/patologia , Eczema/patologia , Administração Tópica , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Idoso , Produtos Biológicos/uso terapêutico , Compostos de Boro/administração & dosagem , Compostos de Boro/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Inibidores de Calcineurina/administração & dosagem , Inibidores de Calcineurina/uso terapêutico , Criança , Pré-Escolar , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/tratamento farmacológico , Dermatite Atópica/diagnóstico , Dermatite Atópica/tratamento farmacológico , Diagnóstico Diferencial , Eczema/diagnóstico , Eczema/tratamento farmacológico , Humanos , Lactente , Pessoa de Meia-Idade , Testes do Emplastro/métodos , Fototerapia/métodos , Qualidade de Vida
4.
Molecules ; 26(10)2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34068970

RESUMO

Due to the complicated pathogenic pathways of coronavirus disease 2019 (COVID-19), related medicinal therapies have remained a clinical challenge. COVID-19 highlights the urgent need to develop mechanistic pathogenic pathways and effective agents for preventing/treating future epidemics. As a result, the destructive pathways of COVID-19 are in the line with clinical symptoms induced by severe acute coronary syndrome (SARS), including lung failure and pneumonia. Accordingly, revealing the exact signaling pathways, including inflammation, oxidative stress, apoptosis, and autophagy, as well as relative representative mediators such as tumor necrosis factor-α (TNF-α), nuclear factor erythroid 2-related factor 2 (Nrf2), Bax/caspases, and Beclin/LC3, respectively, will pave the road for combating COVID-19. Prevailing host factors and multiple steps of SARS-CoV-2 attachment/entry, replication, and assembly/release would be hopeful strategies against COVID-19. This is a comprehensive review of the destructive signaling pathways and host-pathogen interaction of SARS-CoV-2, as well as related therapeutic targets and treatment strategies, including potential natural products-based candidates.


Assuntos
Antivirais/uso terapêutico , Produtos Biológicos/uso terapêutico , /metabolismo , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Humanos
5.
Nat Commun ; 12(1): 3225, 2021 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-34050176

RESUMO

Non-Ribosomal Peptides (NRPs) represent a biomedically important class of natural products that include a multitude of antibiotics and other clinically used drugs. NRPs are not directly encoded in the genome but are instead produced by metabolic pathways encoded by biosynthetic gene clusters (BGCs). Since the existing genome mining tools predict many putative NRPs synthesized by a given BGC, it remains unclear which of these putative NRPs are correct and how to identify post-assembly modifications of amino acids in these NRPs in a blind mode, without knowing which modifications exist in the sample. To address this challenge, here we report NRPminer, a modification-tolerant tool for NRP discovery from large (meta)genomic and mass spectrometry datasets. We show that NRPminer is able to identify many NRPs from different environments, including four previously unreported NRP families from soil-associated microbes and NRPs from human microbiota. Furthermore, in this work we demonstrate the anti-parasitic activities and the structure of two of these NRP families using direct bioactivity screening and nuclear magnetic resonance spectrometry, illustrating the power of NRPminer for discovering bioactive NRPs.


Assuntos
Antibacterianos/isolamento & purificação , Produtos Biológicos/isolamento & purificação , Biologia Computacional/métodos , Descoberta de Drogas/métodos , Peptídeos/isolamento & purificação , Algoritmos , Sequência de Aminoácidos/genética , Antibacterianos/biossíntese , Produtos Biológicos/metabolismo , Conjuntos de Dados como Assunto , Humanos , Espectrometria de Massas , Redes e Vias Metabólicas/genética , Metabolômica/métodos , Metagenômica/métodos , Microbiota/genética , Família Multigênica , Biossíntese Peptídica , Peptídeo Sintases/genética , Peptídeo Sintases/metabolismo , Peptídeos/genética , Peptídeos/metabolismo , Microbiologia do Solo
6.
J Mol Model ; 27(6): 160, 2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-33963942

RESUMO

Coronavirus infectious disease 2019 (COVID-19), a viral infection caused by a novel coronavirus (nCoV), continues to emerge as a serious threat to public health. This pandemic caused by SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) has infected globally with 1,550,000 plus deaths to date, representing a high risk to public health. No effective drug or vaccine is available to curb down this deadly virus. The expedition for searching for a potential drug or vaccine against COVID-19 is of massive potential and favour to the community. This study is focused on finding an effective natural compound that can be processed further into a potential inhibitor to check the activity of SARS-CoV-2 with minimal side effects targeting NSP15 protein, which belongs to the EndoU enzyme family. The natural screening suggested two efficient compounds (PubChem ID: 95372568 and 1776037) with dihydroxyphenyl region of the compound, found to be important in the interaction with the viral protein showing promising activity which may act as a potent lead inhibitory molecule against the virus. In combination with virtual screening, modelling, drug likeliness, molecular docking, and 500 ns cumulative molecular dynamics simulations (100 ns for each complex) along with the decomposition analysis to calculate and confirm the stability and fold, we propose 95372568 and 1776037 as novel compounds of natural origin capable of getting developed into potent lead molecules against SARS-CoV-2 target protein NSP15.


Assuntos
Antivirais/química , Produtos Biológicos/química , Biologia Computacional , Endorribonucleases , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Proteínas não Estruturais Virais , Antivirais/uso terapêutico , Produtos Biológicos/uso terapêutico , Endorribonucleases/química , Humanos , Proteínas não Estruturais Virais/química
7.
Yi Chuan ; 43(5): 459-472, 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-33972216

RESUMO

Zi Cao is an important traditional medicinal plant resource in China. Shikonin and its derivatives, as the purple-red naphthoquinones among natural products of its roots, are commonly used clinically in the treatment of sores and skin inflammations. Over the past few decades, due to their highly effective multiple biological activities, pharmacological effects, good clinical efficacy and high utilization value, shikonin and its derivatives have attracted increasing attention of domestic and foreign researchers. For this reason, the wild plant germplasm resources have been suffering a grievous exploitation, leading to a serious threat to the habitat. With the development of the biosynthesis, molecular metabolism and biotechnology, as well as the continuous innovation of research methods on the biological activities and pharmacological effects of plant natural products, significant progress has been made in the research on the biosynthetic pathways and related regulatory genes of shikonin. The pharmacological action and its mechanism of shikonin have also been deeply elucidated, which greatly promoted the basic research and clinical application development of shikonin. In this review, we briefly introduce and analyze the classification of Zi Cao, structure and composition of natural shikonin and its biosynthesis pathway, functional genes related to the regulation of shikonin biosynthesis, and biological activities and pharmacological functions of shikonin. Finally, we address possible prospective for the trend on the future research and development of natural shikonin and its derivatives, hoping to provide a useful reference for the deep mining and development of medicinal natural products from important Chinese medicinal materials, and to promote the modern development of traditional Chinese medicine.


Assuntos
Produtos Biológicos , Plantas Medicinais , China , Raízes de Plantas , Estudos Prospectivos
8.
Medicine (Baltimore) ; 100(18): e25835, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33950995

RESUMO

BACKGROUND: : The microbiome is important in the development and progression of breast cancer. This study investigated the effects of microbiome derived from Klebsiella on endocrine therapy of breast cancer using MCF7 cells. The bacterial extracellular vesicles (EVs) that affect endocrine therapy were established through experiments focused on tamoxifen efficacy. METHODS: : The microbiomes of breast cancer patients and healthy controls were analyzed using next-generation sequencing. Among microbiome, Klebsiella was selected as the experimental material for the effect on endocrine therapy in MCF7 cells. MCF7 cells were incubated with tamoxifen in the absence/presence of bacterial EVs derived from Klebsiella pneumoniae and analyzed by quantitative real-time polymerase chain reaction and Western blot. RESULTS: : Microbiome derived from Klebsiella is abundant in breast cancer patients especially luminal A subtype compared to healthy controls. The addition of EVs derived from K pneumoniae enhances the anti-hormonal effects of tamoxifen in MCF7 cells. The increased efficacy of tamoxifen is mediated via Cyclin E2 and p-ERK. CONCLUSION: : Based on experiments, the EVs derived from K pneumoniae are important in hormone therapy on MCF7 cells. This result provides new insight into breast cancer mechanisms and hormone therapy using Klebsiella found in the microbiome.


Assuntos
Antineoplásicos Hormonais/farmacologia , Produtos Biológicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Vesículas Extracelulares/metabolismo , Microbioma Gastrointestinal , Antineoplásicos Hormonais/uso terapêutico , Produtos Biológicos/uso terapêutico , Neoplasias da Mama/patologia , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Sinergismo Farmacológico , Feminino , Humanos , Klebsiella pneumoniae/citologia , Klebsiella pneumoniae/metabolismo , Células MCF-7 , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico , Urina/citologia
9.
Zhongguo Zhong Yao Za Zhi ; 46(7): 1717-1726, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33982475

RESUMO

Diaporthe sp. fungi is one of the important sources of active natural products. Polyketides, alkaloids, terpenes, anthraquinones and other types of novel metabolic products are found from this genus, and many of them have significant anti-tumor, antibacterial, anti-hyperlipidemia, inhibition of pulmonary fibrosis, antioxidant and other biological activities. This paper reviewed source, structure and biological activity of natural products from Diaporthe sp. in the past two decades, and provided a reference for in-depth study of natural product of this genus fungus and innovative drug development.


Assuntos
Produtos Biológicos , Policetídeos , Antibacterianos , Produtos Biológicos/farmacologia , Fungos , Terpenos
10.
J Med Food ; 24(5): 517-526, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34009021

RESUMO

The incidence of respiratory diseases, such as asthma, has substantially increased in recent times owing to environmental changes, such as air pollution. Induction of a chronic inflammatory response begins with production of biologically active mediators from the airway epithelium, which attracts and recruits inflammatory cells into the lung airway. In our previous study, we confirmed that Lactobacillus casei HY2782 and Bifidobacterium animalis spp. lactis HY8002 could improve lung inflammation in the COPD animal model. In this study, we investigated the effect of the HY2782 complex against airway hyperresponsiveness by using an ovalbumin (OVA)-induced animal model. An orally administered HY2782 complex on OVA-induced allergic asthma in a BALB/c mouse model was used. The present results showed that the HY2782 complex suppressed total immunoglobulin E in serum and bronchoalveolar lavage fluid (BALF). The cytokine production profile in BALF and serum revealed that the HY2782 complex showed reduced levels of Th2 cytokines among immune factors released due to the elevated allergic response. Levels of inflammatory mediators in BALF, MCP-1, MIP-2, and CXCL-9 were decreased by oral administration of the HY2782 complex. Lower numbers of eosinophils and neutrophils in BALF suggested that inflammation was ameliorated by the HY2782 complex. Histological observation of lung sections also showed infiltration of fewer cells. From results, we suggested that the HY2782 complex effectively responds to improvement of the immune response and airway hypersensitivity reaction because of the anti-inflammatory effect of the Pueraria lobata root extract and antioxidant effect of HY2782.


Assuntos
Produtos Biológicos , Lactobacillales , Animais , Líquido da Lavagem Broncoalveolar , Citocinas , Modelos Animais de Doenças , Pulmão , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina , Células Th2
12.
World J Gastroenterol ; 27(19): 2312-2324, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34040324

RESUMO

Hepatitis B virus reactivation (HBVr) can occur in patients treated with immunosuppressive medications. Risk stratification for HBVr based on hepatitis B virus (HBV) serology and viral load is an important strategy to determine appropriate HBV monitoring and antiviral prophylaxis use. Recent advances in the understanding of pathophysiology of autoimmune diseases have led the development of cytokine-targeted therapies. Tumor necrosis factor (TNF)-α inhibitors have been widely used for patients with inflammatory bowel disease, psoriasis, and rheumatic diseases. Further, the clinical benefits of interleukin (IL)-12/23, IL-17, or Janus kinases inhibitors have been demonstrated in these patients. It is well known that TNF-α inhibitor use can lead to HBVr, however, the risk of HBVr in patients undergoing non-TNF-targeted biologics have not been fully understood. In this review, we discuss the risk of HBVr in patients treated with non-TNF-targeted biologics, and immunological mechanisms of these medications causing HBVr.


Assuntos
Doenças Autoimunes , Produtos Biológicos , Hepatite B , Antivirais/efeitos adversos , Doenças Autoimunes/tratamento farmacológico , Produtos Biológicos/efeitos adversos , Hepatite B/diagnóstico , Hepatite B/tratamento farmacológico , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B , Humanos , Fator de Necrose Tumoral alfa/farmacologia , Ativação Viral
13.
Molecules ; 26(9)2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33946153

RESUMO

Leaves of Lippia thymoides (Verbenaceae) were dried in an oven at 40, 50 and 60 °C and the kinetic of drying and the influence of the drying process on the chemical composition, yield, and DPPH radical scavenging activity of the obtained essential oils were evaluated. The composition of the essential oils was determined with gas chromatography-mass spectrometry and gas chromatography-flame ionization detection analyses. The influence of drying on the chemical composition of the essential oils of L. thymoides was evaluated by multivariate analysis, and their antioxidant activity was investigated via the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The Midilli model was the most appropriate to describe the behavior of drying kinetic data of L. thymoides leaves. Thymol was the major compound for all analyzed conditions; the maximum content was obtained from fresh leaves (62.78 ± 0.63%). The essential oils showed DPPH radical scavenging activity with an average of 73.10 ± 12.08%, and the fresh leaves showed higher inhibition (89.97 ± 0.31%). This is the first study to evaluate the influence of drying on the chemical composition and antioxidant activity of L. thymoides essential oils rich in thymol.


Assuntos
Antioxidantes/química , Lippia/química , Óleos Voláteis/química , Óleos Vegetais/química , Timol/química , Antioxidantes/farmacologia , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Óleos Voláteis/farmacologia , Folhas de Planta/química , Óleos Vegetais/farmacologia , Temperatura , Timol/farmacologia
14.
Molecules ; 26(9)2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33946249

RESUMO

Food processing generates a large amount of bio-residues, which have become the focus of different studies aimed at valorizing this low-cost source of bioactive compounds. High fruit consumption is associated with beneficial health effects and, therefore, bio-waste and its constituents arouse therapeutic interest. The present work focuses on the main Portuguese fruit crops and revises (i) the chemical constituents of apple, orange, and pear pomace as potential sources of functional/bioactive compounds; (ii) the bioactive evidence and potential therapeutic use of bio-waste generated in the processing of the main Portuguese fruit crops; and (iii) potential applications in the food, nutraceutical, pharmaceutical, and cosmetics industries. The current evidence of the effect of these bio-residues as antioxidant, anti-inflammatory, and antimicrobial agents is also summarized. Conclusions of the revised data are that these bio-wastes hold great potential to be employed in specific nutritional and pharmaceutical applications.


Assuntos
Produtos Biológicos/química , Manipulação de Alimentos , Frutas/química , Resíduos , Produtos Biológicos/farmacologia , Cosméticos , Desenvolvimento de Medicamentos , Alimento Funcional , Humanos , Hidrólise , Malus , Estrutura Molecular , Pectinas/química , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Polifenóis/química , Portugal , Pyrus
15.
Molecules ; 26(9)2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33946338

RESUMO

The genus Datura (Solanaceae) contains nine species of medicinal plants that have held both curative utility and cultural significance throughout history. This genus' particular bioactivity results from the enormous diversity of alkaloids it contains, making it a valuable study organism for many disciplines. Although Datura contains mostly tropane alkaloids (such as hyoscyamine and scopolamine), indole, beta-carboline, and pyrrolidine alkaloids have also been identified. The tools available to explore specialized metabolism in plants have undergone remarkable advances over the past couple of decades and provide renewed opportunities for discoveries of new compounds and the genetic basis for their biosynthesis. This review provides a comprehensive overview of studies on the alkaloids of Datura that focuses on three questions: How do we find and identify alkaloids? Where do alkaloids come from? What factors affect their presence and abundance? We also address pitfalls and relevant questions applicable to natural products and metabolomics researchers. With both careful perspectives and new advances in instrumentation, the pace of alkaloid discovery-from not just Datura-has the potential to accelerate dramatically in the near future.


Assuntos
Alcaloides/química , Produtos Biológicos/química , Datura/química , Compostos Fitoquímicos/química , Alcaloides/análise , Alcaloides/isolamento & purificação , Alcaloides/metabolismo , Produtos Biológicos/análise , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/metabolismo , Fracionamento Químico , Fenômenos Químicos , Cromatografia Líquida , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura Molecular , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/metabolismo , Relação Estrutura-Atividade
16.
Molecules ; 26(9)2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33946376

RESUMO

Anthocyanins are naturally occurring phytochemicals that have attracted growing interest from consumers and the food industry due to their multiple biological properties and technological applications. Nevertheless, conventional extraction techniques based on thermal technologies can compromise both the recovery and stability of anthocyanins, reducing their global yield and/or limiting their application in food systems. The current review provides an overview of the main innovative processes (e.g., pulsed electric field, microwave, and ultrasound) used to recover anthocyanins from agri-food waste/by-products and the mechanisms involved in anthocyanin extraction and their impacts on the stability of these compounds. Moreover, trends and perspectives of anthocyanins' applications in food systems, such as antioxidants, natural colorants, preservatives, and active and smart packaging components, are addressed. Challenges behind anthocyanin implementation in food systems are displayed and potential solutions to overcome these drawbacks are proposed.


Assuntos
Antocianinas/química , Antocianinas/isolamento & purificação , Produtos Agrícolas/química , Manipulação de Alimentos , Antocianinas/farmacologia , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Indústria Alimentícia , Concentração de Íons de Hidrogênio , Estrutura Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Relação Estrutura-Atividade
17.
Molecules ; 26(9)2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33946466

RESUMO

The species Pseudogymnoascus is known as a psychrophilic pathogenic fungus which is ubiquitously distributed in Antarctica. While the studies of its secondary metabolites are infrequent. Systematic research of the metabolites of the Antarctic fungus Pseudogymnoascus sp. HSX2#-11 led to the isolation of one new pyridine derivative, 4-(2-methoxycarbonyl-ethyl)-pyridine-2-carboxylic acid methyl ester (1), together with one pyrimidine, thymine (2), and eight diketopiperazines, cyclo-(dehydroAla-l-Val) (3), cyclo-(dehydroAla-l-Ile) (4), cyclo-(dehydroAla-l-Leu) (5), cyclo-(dehydroAla-l-Phe) (6), cyclo-(l-Val-l-Phe) (7), cyclo-(l-Leu-l-Phe) (8), cyclo-(l-Trp-l-Ile) (9) and cyclo-(l-Trp-l-Phe) (10). The structures of these compounds were established by extensive spectroscopic investigation, as well as by detailed comparison with literature data. This is the first report to discover pyridine, pyrimidine and diketopiperazines from the genus of Pseudogymnoascus.


Assuntos
Ascomicetos/química , Compostos de Nitrogênio/análise , Regiões Antárticas , Ascomicetos/metabolismo , Produtos Biológicos/química , Estrutura Molecular , Compostos de Nitrogênio/química , Metabolismo Secundário
18.
Molecules ; 26(9)2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33946559

RESUMO

Alzheimer's disease (AD) is the most common form of dementia and is characterized by irreversible and progressive neurodegeneration. Cholinergic dysfunction has been reported in AD, and several cholinesterase inhibitors, including natural compounds and synthetic analogs, have been developed to treat the disease. However, there is currently no treatment for AD, as most drug-like compounds have failed in clinical trials. Acetylcholinesterase (AChE) is the target of most drugs used commercially to treat AD. This work focused on screening natural compounds obtained from the ZINC database (224, 205 compounds) against AChE to identify those possibly capable of enabling the management of AD. Indirubin and dehydroevodiamine were the best potential AChE inhibitors with free binding energies of -10.03 and -9.00 kcal/mol, respectively. The key residue (His447) of the active site of AChE was found to participate in complex interactions with these two molecules. Six H-bonds were involved in the 'indirubin-AChE' interaction and three H-bonds in the 'dehydroevodiamine-AChE' interaction. These compounds were predicted to cross the blood-brain barrier (BBB) and to exhibit high levels of intestinal absorption. Furthermore, 'indirubin-AChE' and 'dehydroevodiamine-AChE' complexes were found to be stable, as determined by root mean square deviation (RMSD) during a 50 ns molecular dynamics simulation study. Based on the free binding energies and stabilities obtained by simulation studies, we recommend that experimental studies be undertaken on indirubin and dehydroevodiamine with a view towards their potential use as treatments for AD.


Assuntos
Acetilcolinesterase/química , Produtos Biológicos/química , Inibidores da Colinesterase/química , Biologia Computacional/métodos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Doença de Alzheimer/tratamento farmacológico , Sítios de Ligação , Produtos Biológicos/farmacologia , Inibidores da Colinesterase/farmacologia , Bases de Dados de Produtos Farmacêuticos , Humanos , Estrutura Molecular , Ligação Proteica , Conformação Proteica , Relação Estrutura-Atividade
19.
Molecules ; 26(9)2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33946573

RESUMO

The present study aimed to evaluate the effect of Jerusalem artichoke processing methods and drying methods (freeze drying, sublimation drying, vacuum drying) on the basic physicochemical parameters, profiles and contents of sugars and polyphenolic compounds, and health-promoting properties (antioxidant activity, inhibition of the activities of α-amylase, α-glucosidase, and pancreatic lipase) of the produced purée. A total of 25 polyphenolic compounds belonging to hydroxycinnamic phenolic acids (LC-PDA-MS-QTof) were detected in Jerusalem artichoke purée. Their average content in the raw material was at 820 mg/100 g dm (UPLC-PDA-FL) and was 2.7 times higher than in the cooked material. The chemical composition and the health-promoting value of the purées were affected by the drying method, with the most beneficial values of the evaluated parameters obtained upon freeze drying. Vacuum drying could offer an alternative to freeze drying, as both methods ensured relatively comparable values of the assessed parameters.


Assuntos
Fenômenos Químicos , Alimento Funcional/análise , Helianthus/química , Extratos Vegetais/química , Antioxidantes/química , Antioxidantes/farmacologia , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Cromatografia Líquida de Alta Pressão , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Polifenóis/química , Açúcares/química
20.
Molecules ; 26(9)2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33946576

RESUMO

Some medicines are poorly soluble in water. For tube feeding and parenteral administration, liquid formulations are required. The discovery of natural deep eutectic solvents (NADES) opened the way to potential applications for liquid drug formulations. NADES consists of a mixture of two or more simple natural products such as sugars, amino acids, organic acids, choline/betaine, and poly-alcohols in certain molar ratios. A series of NADES with a water content of 0-30% (w/w) was screened for the ability to solubilize (in a stable way) some poorly water-soluble pharmaceuticals at a concentration of 5 mg/mL. The results showed that NADES selectively dissolved the tested drugs. Some mixtures of choline-based NADES, acid-neutral or sugars-based NADES could dissolve chloral hydrate (dissociated in water), ranitidine·HCl (polymorphism), and methylphenidate (water insoluble), at a concentration of up to 250 mg/mL, the highest concentration tested. Whereas a mixture of lactic-acid-propyleneglycol could dissolve spironolacton and trimethoprim at a concentration up to 50 and 100 mg/mL, respectively. The results showed that NADES are promising solvents for formulation of poorly water-soluble medicines for the development of parenteral and tube feeding administration of non-water-soluble medicines. The chemical stability and bioavailability of these drug in NADES needs further studies.


Assuntos
Produtos Biológicos/química , Composição de Medicamentos , Preparações Farmacêuticas/química , Solventes/química , Betaína/química , Colina/química , Estabilidade de Medicamentos , Concentração de Íons de Hidrogênio , Estrutura Molecular , Solubilidade
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