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1.
Molecules ; 25(17)2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32882868

RESUMO

Over the years, coronaviruses (CoV) have posed a severe public health threat, causing an increase in mortality and morbidity rates throughout the world. The recent outbreak of a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the current Coronavirus Disease 2019 (COVID-19) pandemic that affected more than 215 countries with over 23 million cases and 800,000 deaths as of today. The situation is critical, especially with the absence of specific medicines or vaccines; hence, efforts toward the development of anti-COVID-19 medicines are being intensively undertaken. One of the potential therapeutic targets of anti-COVID-19 drugs is the angiotensin-converting enzyme 2 (ACE2). ACE2 was identified as a key functional receptor for CoV associated with COVID-19. ACE2, which is located on the surface of the host cells, binds effectively to the spike protein of CoV, thus enabling the virus to infect the epithelial cells of the host. Previous studies showed that certain flavonoids exhibit angiotensin-converting enzyme inhibition activity, which plays a crucial role in the regulation of arterial blood pressure. Thus, it is being postulated that these flavonoids might also interact with ACE2. This postulation might be of interest because these compounds also show antiviral activity in vitro. This article summarizes the natural flavonoids with potential efficacy against COVID-19 through ACE2 receptor inhibition.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/fisiologia , Produtos Biológicos/farmacologia , Infecções por Coronavirus/virologia , Flavonoides/farmacologia , Pneumonia Viral/virologia , Inibidores da Enzima Conversora de Angiotensina/química , Antivirais/química , Produtos Biológicos/química , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Suscetibilidade a Doenças , Flavonoides/química , Humanos , Estágios do Ciclo de Vida , Modelos Moleculares , Pandemias , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Vigilância da População , Relação Estrutura-Atividade
2.
Molecules ; 25(17)2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: covidwho-742825

RESUMO

Over the years, coronaviruses (CoV) have posed a severe public health threat, causing an increase in mortality and morbidity rates throughout the world. The recent outbreak of a novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the current Coronavirus Disease 2019 (COVID-19) pandemic that affected more than 215 countries with over 23 million cases and 800,000 deaths as of today. The situation is critical, especially with the absence of specific medicines or vaccines; hence, efforts toward the development of anti-COVID-19 medicines are being intensively undertaken. One of the potential therapeutic targets of anti-COVID-19 drugs is the angiotensin-converting enzyme 2 (ACE2). ACE2 was identified as a key functional receptor for CoV associated with COVID-19. ACE2, which is located on the surface of the host cells, binds effectively to the spike protein of CoV, thus enabling the virus to infect the epithelial cells of the host. Previous studies showed that certain flavonoids exhibit angiotensin-converting enzyme inhibition activity, which plays a crucial role in the regulation of arterial blood pressure. Thus, it is being postulated that these flavonoids might also interact with ACE2. This postulation might be of interest because these compounds also show antiviral activity in vitro. This article summarizes the natural flavonoids with potential efficacy against COVID-19 through ACE2 receptor inhibition.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/fisiologia , Produtos Biológicos/farmacologia , Infecções por Coronavirus/virologia , Flavonoides/farmacologia , Pneumonia Viral/virologia , Inibidores da Enzima Conversora de Angiotensina/química , Antivirais/química , Produtos Biológicos/química , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Suscetibilidade a Doenças , Flavonoides/química , Humanos , Estágios do Ciclo de Vida , Modelos Moleculares , Pandemias , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Vigilância da População , Relação Estrutura-Atividade
3.
Anticancer Res ; 40(9): 5201-5210, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878808

RESUMO

BACKGROUND/AIM: Persimmon (Diospyros kaki L.) leaves are popular as a tea infusion in Asia and their main active ingredients are flavonoids. The present study aimed to explore the anticancer properties of flavonoids isolated from persimmon leaves (PLF). MATERIALS AND METHODS: We investigated the in vitro anti-proliferative activity of PLF against several human cancer cell lines. Apoptosis and intracellular reactive oxygen species (ROS) induced by PLF were accessed using high-content analysis with florescent staining. The ability of PLF to scavenge free radicals was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. RESULTS: PLF demonstrated significant inhibition of proliferation of liver, breast, and colorectal cancer cells in vitro. PLF induced apoptosis and increased intracellular ROS levels in HCT116 (colorectal cancer) and HepG2 (liver cancer) cells. In addition, PLF showed strong free radical scavenging ability. CONCLUSION: The anti-proliferation activity of PLF against cancer cells was related to the induction of apoptosis and oxidative stress.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Diospyros/química , Flavonoides/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antioxidantes/química , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Flavonoides/química , Flavonoides/isolamento & purificação , Humanos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Espécies Reativas de Oxigênio/metabolismo
4.
Acta Pharmacol Sin ; 41(9): 1167-1177, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32737471

RESUMO

Human infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and there is no cure currently. The 3CL protease (3CLpro) is a highly conserved protease which is indispensable for CoVs replication, and is a promising target for development of broad-spectrum antiviral drugs. In this study we investigated the anti-SARS-CoV-2 potential of Shuanghuanglian preparation, a Chinese traditional patent medicine with a long history for treating respiratory tract infection in China. We showed that either the oral liquid of Shuanghuanglian, the lyophilized powder of Shuanghuanglian for injection or their bioactive components dose-dependently inhibited SARS-CoV-2 3CLpro as well as the replication of SARS-CoV-2 in Vero E6 cells. Baicalin and baicalein, two ingredients of Shuanghuanglian, were characterized as the first noncovalent, nonpeptidomimetic inhibitors of SARS-CoV-2 3CLpro and exhibited potent antiviral activities in a cell-based system. Remarkably, the binding mode of baicalein with SARS-CoV-2 3CLpro determined by X-ray protein crystallography was distinctly different from those of known 3CLpro inhibitors. Baicalein was productively ensconced in the core of the substrate-binding pocket by interacting with two catalytic residues, the crucial S1/S2 subsites and the oxyanion loop, acting as a "shield" in front of the catalytic dyad to effectively prevent substrate access to the catalytic dyad within the active site. Overall, this study provides an example for exploring the in vitro potency of Chinese traditional patent medicines and effectively identifying bioactive ingredients toward a specific target, and gains evidence supporting the in vivo studies of Shuanghuanglian oral liquid as well as two natural products for COVID-19 treatment.


Assuntos
Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus , Medicamentos de Ervas Chinesas , Flavanonas , Flavonoides , Pandemias , Pneumonia Viral , Replicação Viral/efeitos dos fármacos , Administração Oral , Animais , Antivirais/química , Antivirais/farmacologia , Betacoronavirus/fisiologia , Chlorocebus aethiops , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Ensaios Enzimáticos , Flavanonas/química , Flavanonas/farmacocinética , Flavonoides/química , Flavonoides/farmacocinética , Humanos , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Células Vero , Replicação Viral/fisiologia
5.
J Enzyme Inhib Med Chem ; 35(1): 1539-1544, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32746637

RESUMO

Coronavirus disease 2019 (COVID-19) has been a pandemic disease of which the termination is not yet predictable. Currently, researches to develop vaccines and treatments is going on globally to cope with this disastrous disease. Main protease (3CLpro) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the good targets to find antiviral agents before vaccines are available. Some flavonoids are known to inhibit 3CLpro from SARS-CoV which causes SARS. Since their sequence identity is 96%, a similar approach was performed with a flavonoid library. Baicalin, herbacetin, and pectolinarin have been discovered to block the proteolytic activity of SARS-CoV-2 3CLpro. An in silico docking study showed that the binding modes of herbacetin and pectolinarin are similar to those obtained from the catalytic domain of SARS-CoV 3CLpro. However, their binding affinities are different due to the usage of whole SARS-CoV-2 3CLpro in this study. Baicalin showed an effective inhibitory activity against SARS-CoV-2 3CLpro and its docking mode is different from those of herbacetin and pectolinarin. This study suggests important scaffolds to design 3CLpro inhibitors to develop antiviral agents or health-foods and dietary supplements to cope with SARS-CoV-2.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Flavonoides/química , Pneumonia Viral/tratamento farmacológico , Proteínas Virais/antagonistas & inibidores , Proteínas Virais/química , Antivirais/química , Betacoronavirus , Desenho de Fármacos , Transferência Ressonante de Energia de Fluorescência , Humanos , Simulação de Acoplamento Molecular , Pandemias , Inibidores de Proteases/química , Ligação Proteica , Conformação Proteica , Espectrofotometria , Triptofano/química
6.
Chem Biol Interact ; 328: 109211, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32735799

RESUMO

In terms of public health, the 21st century has been characterized by coronavirus pandemics: in 2002-03 the virus SARS-CoV caused SARS; in 2012 MERS-CoV emerged and in 2019 a new human betacoronavirus strain, called SARS-CoV-2, caused the unprecedented COVID-19 outbreak. During the course of the current epidemic, medical challenges to save lives and scientific research aimed to reveal the genetic evolution and the biochemistry of the vital cycle of the new pathogen could lead to new preventive and therapeutic strategies against SARS-CoV-2. Up to now, there is no cure for COVID-19 and waiting for an efficacious vaccine, the development of "savage" protocols, based on "old" anti-inflammatory and anti-viral drugs represents a valid and alternative therapeutic approach. As an alternative or additional therapeutic/preventive option, different in silico and in vitro studies demonstrated that small natural molecules, belonging to polyphenol family, can interfere with various stages of coronavirus entry and replication cycle. Here, we reviewed the capacity of well-known (e.g. quercetin, baicalin, luteolin, hesperetin, gallocatechin gallate, epigallocatechin gallate) and uncommon (e.g. scutellarein, amentoflavone, papyriflavonol A) flavonoids, secondary metabolites widely present in plant tissues with antioxidant and anti-microbial functions, to inhibit key proteins involved in coronavirus infective cycle, such as PLpro, 3CLpro, NTPase/helicase. Due to their pleiotropic activities and lack of systemic toxicity, flavonoids and their derivative may represent target compounds to be tested in future clinical trials to enrich the drug arsenal against coronavirus infections.


Assuntos
Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Flavonoides/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Animais , Antivirais/química , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/genética , Betacoronavirus/fisiologia , Simulação por Computador , Coronaviridae/efeitos dos fármacos , Coronaviridae/fisiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Avaliação Pré-Clínica de Medicamentos , Flavonoides/química , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Vírus da SARS/efeitos dos fármacos , Proteínas Virais/antagonistas & inibidores , Replicação Viral/efeitos dos fármacos
7.
J Chromatogr A ; 1628: 461446, 2020 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-32822985

RESUMO

Ionic liquids, as tuneable, highly soluble, non-flammable, non-volatile and reusable extractants, have attracted extensive attention in the extraction of flavonoids from plants. In the present work, novel dual-chain imidazolium-derived ionic liquids were synthesized by a simple and efficient method and characterized (NMR spectroscopy, thermal stability, viscosity, conductivity, and polarity). Then, the imidazolium ionic liquids with different cation were used in the microwave-assisted extraction of flavonoids from Pinus massoniana Lamb. The results showed that the ionic liquid [Bmbim]Br, with a relatively low viscosity, conductivity and π* as well as a relatively large ß, offered the best extraction efficiency and selectivity for flavonoids. Subsequently, the parameters of the extraction procedure for flavonoids were optimized as follows: extraction temperature of 80 °C, extraction time of 60 min, microwave power of 300 W, solid-liquid ratio of 1:20, and [Bmbim]Br solution concentration of 1.0 mol/L. The extraction yield of total flavonoids was 41.07 mg/g. Finally, a recovery method of the ionic liquid had been demonstrated, and the recovery rate of ionic liquid was 73.14%.


Assuntos
Flavonoides/isolamento & purificação , Líquidos Iônicos/síntese química , Cátions , Flavonoides/química , Micro-Ondas , Pinus/química , Extratos Vegetais/química
8.
Life Sci ; 258: 118211, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32768576

RESUMO

AIMS: Cisplatin is the mainstay of first-line treatment for advanced non-small cell lung cancer (NSCLC). Accumulating evidence suggests that flavonoids inhibit histone deacetylase (HDAC) to mediate their anticancer effect in various cancer types. The study was conducted to investigate the inhibition of HDAC and the modulation of apoptotic and cell cycle regulatory genes by selected flavonoids to potentiate the anticancer effect of cisplatin. MAIN METHODS: Combinations of cisplatin and selected flavonoids were investigated in three NSCLC cell lines (A549, H460, and H1299). Sulforhodamine B assay was used to evaluate cytotoxicity of drug combinations. Western blot analysis was conducted to evaluate histone acetylation. Flow cytometric assays were used to investigate the apoptotic and cell cycle effect. Chromatin immunoprecipitation assay was performed to elucidate the binding of transcription factors to promoters of selected apoptotic and cell cycle regulatory genes. KEY FINDINGS: Apigenin was found to exhibit the strongest HDAC inhibitory effect among all flavonoids tested. Cisplatin-apigenin combination was shown to produce significantly more S phase prolongation and G2/M cell cycle arrest, and apoptosis compared with cisplatin or apigenin alone, by inducing p21 and PUMA, respectively. More pronounced effect was observed in p53-proficient than p53-null NSCLC cells. Mechanistically, apigenin was found to reduce the binding of HDAC1 but increase the association of RNA polymerase II and Sp1 to p21 and PUMA promoters. SIGNIFICANCE: Our findings provide a better insight about the mechanism contributing to the HDAC inhibitory effect of apigenin to potentiate anticancer effect of cisplatin by inducing apoptosis and cell cycle arrest.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Cisplatino/administração & dosagem , Flavonoides/administração & dosagem , Inibidores de Histona Desacetilases/administração & dosagem , Neoplasias Pulmonares/enzimologia , Células A549 , Antineoplásicos/química , Apigenina/administração & dosagem , Apigenina/química , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Cisplatino/química , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Flavonoides/química , Inibidores de Histona Desacetilases/química , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia
9.
J Enzyme Inhib Med Chem ; 35(1): 1539-1544, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: covidwho-694175

RESUMO

Coronavirus disease 2019 (COVID-19) has been a pandemic disease of which the termination is not yet predictable. Currently, researches to develop vaccines and treatments is going on globally to cope with this disastrous disease. Main protease (3CLpro) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the good targets to find antiviral agents before vaccines are available. Some flavonoids are known to inhibit 3CLpro from SARS-CoV which causes SARS. Since their sequence identity is 96%, a similar approach was performed with a flavonoid library. Baicalin, herbacetin, and pectolinarin have been discovered to block the proteolytic activity of SARS-CoV-2 3CLpro. An in silico docking study showed that the binding modes of herbacetin and pectolinarin are similar to those obtained from the catalytic domain of SARS-CoV 3CLpro. However, their binding affinities are different due to the usage of whole SARS-CoV-2 3CLpro in this study. Baicalin showed an effective inhibitory activity against SARS-CoV-2 3CLpro and its docking mode is different from those of herbacetin and pectolinarin. This study suggests important scaffolds to design 3CLpro inhibitors to develop antiviral agents or health-foods and dietary supplements to cope with SARS-CoV-2.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Flavonoides/química , Pneumonia Viral/tratamento farmacológico , Proteínas Virais/antagonistas & inibidores , Proteínas Virais/química , Antivirais/química , Betacoronavirus , Desenho de Fármacos , Transferência Ressonante de Energia de Fluorescência , Humanos , Simulação de Acoplamento Molecular , Pandemias , Inibidores de Proteases/química , Ligação Proteica , Conformação Proteica , Espectrofotometria , Triptofano/química
10.
Chem Biol Interact ; 328: 109211, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: covidwho-679712

RESUMO

In terms of public health, the 21st century has been characterized by coronavirus pandemics: in 2002-03 the virus SARS-CoV caused SARS; in 2012 MERS-CoV emerged and in 2019 a new human betacoronavirus strain, called SARS-CoV-2, caused the unprecedented COVID-19 outbreak. During the course of the current epidemic, medical challenges to save lives and scientific research aimed to reveal the genetic evolution and the biochemistry of the vital cycle of the new pathogen could lead to new preventive and therapeutic strategies against SARS-CoV-2. Up to now, there is no cure for COVID-19 and waiting for an efficacious vaccine, the development of "savage" protocols, based on "old" anti-inflammatory and anti-viral drugs represents a valid and alternative therapeutic approach. As an alternative or additional therapeutic/preventive option, different in silico and in vitro studies demonstrated that small natural molecules, belonging to polyphenol family, can interfere with various stages of coronavirus entry and replication cycle. Here, we reviewed the capacity of well-known (e.g. quercetin, baicalin, luteolin, hesperetin, gallocatechin gallate, epigallocatechin gallate) and uncommon (e.g. scutellarein, amentoflavone, papyriflavonol A) flavonoids, secondary metabolites widely present in plant tissues with antioxidant and anti-microbial functions, to inhibit key proteins involved in coronavirus infective cycle, such as PLpro, 3CLpro, NTPase/helicase. Due to their pleiotropic activities and lack of systemic toxicity, flavonoids and their derivative may represent target compounds to be tested in future clinical trials to enrich the drug arsenal against coronavirus infections.


Assuntos
Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Flavonoides/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Animais , Antivirais/química , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/genética , Betacoronavirus/fisiologia , Simulação por Computador , Coronaviridae/efeitos dos fármacos , Coronaviridae/fisiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Avaliação Pré-Clínica de Medicamentos , Flavonoides/química , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Vírus da SARS/efeitos dos fármacos , Proteínas Virais/antagonistas & inibidores , Replicação Viral/efeitos dos fármacos
11.
Acta Pharmacol Sin ; 41(9): 1167-1177, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: covidwho-691161

RESUMO

Human infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and there is no cure currently. The 3CL protease (3CLpro) is a highly conserved protease which is indispensable for CoVs replication, and is a promising target for development of broad-spectrum antiviral drugs. In this study we investigated the anti-SARS-CoV-2 potential of Shuanghuanglian preparation, a Chinese traditional patent medicine with a long history for treating respiratory tract infection in China. We showed that either the oral liquid of Shuanghuanglian, the lyophilized powder of Shuanghuanglian for injection or their bioactive components dose-dependently inhibited SARS-CoV-2 3CLpro as well as the replication of SARS-CoV-2 in Vero E6 cells. Baicalin and baicalein, two ingredients of Shuanghuanglian, were characterized as the first noncovalent, nonpeptidomimetic inhibitors of SARS-CoV-2 3CLpro and exhibited potent antiviral activities in a cell-based system. Remarkably, the binding mode of baicalein with SARS-CoV-2 3CLpro determined by X-ray protein crystallography was distinctly different from those of known 3CLpro inhibitors. Baicalein was productively ensconced in the core of the substrate-binding pocket by interacting with two catalytic residues, the crucial S1/S2 subsites and the oxyanion loop, acting as a "shield" in front of the catalytic dyad to effectively prevent substrate access to the catalytic dyad within the active site. Overall, this study provides an example for exploring the in vitro potency of Chinese traditional patent medicines and effectively identifying bioactive ingredients toward a specific target, and gains evidence supporting the in vivo studies of Shuanghuanglian oral liquid as well as two natural products for COVID-19 treatment.


Assuntos
Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus , Medicamentos de Ervas Chinesas , Flavanonas , Flavonoides , Pandemias , Pneumonia Viral , Replicação Viral/efeitos dos fármacos , Administração Oral , Animais , Antivirais/química , Antivirais/farmacologia , Betacoronavirus/fisiologia , Chlorocebus aethiops , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Ensaios Enzimáticos , Flavanonas/química , Flavanonas/farmacocinética , Flavonoides/química , Flavonoides/farmacocinética , Humanos , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Células Vero , Replicação Viral/fisiologia
12.
Acta Crystallogr C Struct Chem ; 76(Pt 8): 723-733, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32756034

RESUMO

The present study examines a series of six biologically-active flavonoid and chromanone derivatives by X-ray crystal structure analysis: (E)-3-benzylidene-2-phenylchroman-4-one, C22H16O2, I, (E)-3-(4-methylbenzylidene)-2-phenylchroman-4-one, C23H18O2, II, (E)-3-(3-methylbenzylidene)-2-phenylchroman-4-one, C23H18O2, III, (E)-3-(4-methoxybenzylidene)-2-phenylchroman-4-one, C23H18O3, IV, (E)-3-benzylidenechroman-4-one, C16H12O2, V, and (E)-3-(4-methoxybenzylidene)chroman-4-one, C17H14O3, VI. The cytotoxic activities of the presented crystal structures have been determined, together with their intermolecular interaction preferences and Hirshfeld surface characteristics. An inverse relationship was found between the contribution of C...C close contacts to the Hirshfeld surface and cytotoxic activity against the WM-115 cancer line. Dependence was also observed between the logP value and the percentage contribution of C...H contacts to the Hirshfeld surface.


Assuntos
Antineoplásicos/farmacologia , Cromanos/química , Citotoxinas/farmacologia , Flavonoides/química , Antineoplásicos/química , Cristalografia por Raios X , Citotoxinas/química , Ligação de Hidrogênio
13.
Anticancer Res ; 40(8): 4547-4556, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727785

RESUMO

BACKGROUND/AIM: Phosphatidyl-inositol-3-kinase (PI3K), a cancer therapeutic target, has been exploited for cancer therapy. The natural compounds flavonoids have increasingly been shown to possess anticancer activity. The current study aimed to explore all known flavonoids for their ability to inhibit PI3Kγ. MATERIALS AND METHODS: Virtual screening of flavonoids using molecular docking to the ATP binding site of PI3Kγ was performed. The top 10 scoring flavonoids were selected for pose analysis and binding strength scores. RESULTS: Molecular docking revealed that the 10 selected flavonoids might inhibit PI3Kγ kinase activity. Literature search did not identify studies reporting a bioassay activity for any of these compounds. CONCLUSION: All 10 selected flavonoids are potential PI3Kγ kinase inhibitors and anticancer agents. Interestingly, one of the 10 least scoring flavonoids has been reported to be inactive, as expected, and thus validating the accuracy of the results.


Assuntos
Classe Ib de Fosfatidilinositol 3-Quinase/química , Classe Ib de Fosfatidilinositol 3-Quinase/metabolismo , Flavonoides/farmacologia , Neoplasias/enzimologia , Sítios de Ligação , Simulação por Computador , Regulação para Baixo , Ensaios de Seleção de Medicamentos Antitumorais , Flavonoides/química , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Modelos Moleculares , Simulação de Acoplamento Molecular , Estrutura Molecular , Neoplasias/tratamento farmacológico
14.
PLoS One ; 15(7): e0236565, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32730299

RESUMO

Flavonoids are key components of licorice plant that directly affect its medicinal quality. Importantly, the MYB family of transcription factors serves to regulate the synthesis of flavonoids in plants. The MYB transcription factors represent one of the largest families of transcription factors in plants and play important roles in the process of plant growth and development. MYB gene expression is induced by a number of plant hormones, including the lipid-based hormone jasmonate (JA). Methyl jasmonate (MeJA) is an endogenous plant growth regulator that can induce the JA signaling pathway, which functions to regulate the synthesis of secondary metabolites, including flavonoids. In this study, MeJA was added to licorice cell suspensions, and RNA-seq analysis was performed to identify the differentially expressed genes. As a result, the MYB transcription factors GlMYB4 and GlMYB88 were demonstrated to respond significantly to MeJA induction. Subsequently, the GlMYB4 and GlMYB88 protein were shown to localize to the cell nucleus, and it was verified that GlMYB4 and GlMYB88 could positively regulate the synthesis of flavonoids in licorice cells. Overall, this research helps illustrate the molecular regulation of licorice flavonoid biosynthesis induced by MeJA.


Assuntos
Acetatos/farmacologia , Ciclopentanos/farmacologia , Flavonoides/biossíntese , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Glycyrrhiza uralensis/metabolismo , Oxilipinas/farmacologia , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Flavonoides/química , Glycyrrhiza uralensis/química , Glycyrrhiza uralensis/crescimento & desenvolvimento , Filogenia , Folhas de Planta/metabolismo , Proteínas de Plantas/classificação , Proteínas de Plantas/genética , Raízes de Plantas/metabolismo , Caules de Planta/metabolismo , Fatores de Transcrição/classificação , Fatores de Transcrição/genética
15.
J Nat Med ; 74(4): 750-757, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32621255

RESUMO

Artemisia sieversiana is an annual herbaceous plant distributed throughout Central and East Eurasia and is regarded as an undesirable forage plant in Mongolia. It affects livestock, so information about its chemical composition is needed. We isolated three new sesquiterpenoids (1-3) and known compounds from A. sieversiana and investigated their activities. The absolute configuration of 1 was established using single-crystal X-ray diffraction crystallography, and its configuration differed from those of reported compounds with similar structures. Two additional new sesquiterpenoids (2 and 3) with similar structures were identified, and their configurations were determined. The trypanocidal activities of the isolated compounds (1-18) against Trypanosoma congolense and the pathogen responsible for fatal trypanosomosis in animals were estimated. Flavonoids and lignans were identified as active compounds with IC50 values ranging from 2.9 to 90.2 µM.


Assuntos
Artemisia/química , Flavonoides/química , Lignanas/química , Plantas/química , Sesquiterpenos/química , Estrutura Molecular , Mongólia
16.
An Acad Bras Cienc ; 92(1): e20190819, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32491127

RESUMO

Herbal-flavonoids (HF) as polyphenolic secondary metabolites are taken in the daily diet to join in many metabolic processes in the human organism. Anti-proliferative activities and human serum albumin (HSA) binding capacities of herbal-flavonoids namely 7,5'-dimethoxyisoetin (HF1), homoorientin-6''-4-O-methyl-myo-inositol (HF2), (2R, 3R)-(+)-dihydrokaempferol-7,4'-dimethylether (HF3), eriodictyol-7,4'-dimethylether (HF4) and flavonoids isoorientin (HF5) and genkwanin (HF6) were investigated. Anti-proliferative activities were determined by the xCELLigence system by treatment with human prostate (PC3) and cervical cancer (HeLa) cells. The binding capacities were studied by two-dimensional (2D-FL) and three-dimensional (3D-FL) fluorescence spectroscopy. HeLa and PC3 cell lines were treated with flavonoids at 10, 50 and 100 µg/mL concentrations over a 48 hour period. Stable anti-proliferative efficacy plots were obtained for tested flavonoids. From the flavonoids, HF3 and HF4 showed the strongest anti-proliferative effect against PC3 and HeLa cell line. HF1 and HF2 exhibited the strongest binding capacity to the HSA corresponding to Kb values of 3.81 x 104 M-1 and 6.00 x 104 M-1, respectively. The studies revealed that the flavonoids form the basis of in vivo preclinical studies as important nutraceuticals of the daily diet, as well as modelled in medical and pharmacological applications.


Assuntos
Proliferação de Células/efeitos dos fármacos , Flavonoides/farmacologia , Albumina Sérica Humana/efeitos dos fármacos , Flavonoides/química , Células HeLa , Humanos , Espectrometria de Fluorescência
17.
Food Chem ; 330: 127244, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32526652

RESUMO

The aim of this study is to simultaneously evaluate anti-oxidative and anti-inflammatory activities of the hop extracts by different solvents. Hop water extract (HWE) and hop ethanol extracts (HEEs) were prepared by extracting hop pellets with hot water at 90 °C and ethanol solutions (55%, 75%, and 95%), respectively. Bioactive compound such as α-acid, ß-acid, total phenolic, and total flavonoid contents were determined. All the HEEs showed higher anti-oxidative activities than the HWEs. The HEEs showing the highest anti-oxidative activities are different in the experiments with different free radicals. For anti-inflammatory activities, both the HWE and HEEs decreased NO productions. HWE decreased TNF-α and IL-6 secretion but showed no effect on IL-1ß, while HEEs decreased IL-1ß and IL-6 secretion but increased TNF-α secretion. Except for TNF-α secretion, the HEEs showed higher anti-inflammatory activities than the HWE. Future work is to explore the possible mechanism to improve the ethanol extraction procedure.


Assuntos
Anti-Inflamatórios/química , Antioxidantes/química , Humulus/química , Extratos Vegetais/química , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Flavonoides/química , Camundongos , Oxirredução , Fenóis/química , Extratos Vegetais/farmacologia
18.
Food Chem ; 330: 127222, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32521400

RESUMO

Complete characterization of microfiltered red-purple pitaya colorant (MRPPC) and its potential applications in foods is described. Using sensorial analysis, products that use carmine or beetroot dye as a food colorant in their formulations were compared. The effect of storage under refrigeration on the microbiological, physicochemical, and chemical changes of MRPPC were evaluated. The results showed that UPLC-ESI-QTOF-MSE was effective for the simultaneous determination of twenty metabolites, putatively identified as carbohydrates, flavonoids, and betalains. The MRPPC was shown to have microbiological and physicochemical stability through twelve weeks of storage, and chemometric analyses efficiently distinguished the metabolic profile in each storage period. Sensory analysis revealed that the MRPPC was useful as a food colorant in yogurt, where it improved color quality without affecting aroma and other characteristics. These results indicate that MRPPC is promising food ingredient as a natural red-purple colorant.


Assuntos
Cactaceae/metabolismo , Ingredientes de Alimentos/análise , Antioxidantes/química , Cactaceae/química , Cromatografia Líquida de Alta Pressão , Cor , Flavonoides/química , Metaboloma , Extratos Vegetais/química , Espectrometria de Massas por Ionização por Electrospray
19.
Food Chem ; 330: 127211, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32540527

RESUMO

With the current agro-food industry demands for more environmentally-friendly production, the use of natural antifungal compounds extracted by emerging technologies led to a sustainable alternative to control microorganisms. Therefore, the present work aimed to: (i) determine antifungal activity against Colletotrichum gloeosporioides and Penicillium italicum of jackfruit leaf extracts obtained by different methods, and (ii) identify compounds by HPLC-DAD-ESI-MS. Microwave (MAE), high-hydrostatic pressure (HHP) and ultrasound (UAE) assisted extractions were tested, followed by fractionation with different polarity solvents. The concentration of total soluble phenols (TSP), tannins (TT) and flavonoids (TF) were determined. Differences not only in the amounts of extracted phytochemicals were found but in the antifungal properties (MAE against P. italicum and HHP against C. gloeosporioides at 5 mg/ml) as well as in the chemical composition determined by HPLC-MS. These results suggest the possible application of jackfruit leaf extracts as a suitable postharvest antifungal treatment.


Assuntos
Antifúngicos/química , Artocarpus/química , Compostos Fitoquímicos/química , Extratos Vegetais/química , Antifúngicos/farmacologia , Colletotrichum/efeitos dos fármacos , Flavonoides/química , Penicillium/efeitos dos fármacos , Fenóis/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta/química , Taninos/química
20.
Clin Sci (Lond) ; 134(12): 1403-1432, 2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32556180

RESUMO

Flavonoids are polyphenolic compounds naturally occurring in fruits and vegetables, in addition to beverages such as tea and coffee. Flavonoids are emerging as potent therapeutic agents for cardiovascular as well as metabolic diseases. Several studies corroborated an inverse relationship between flavonoid consumption and cardiovascular disease (CVD) or adipose tissue inflammation (ATI). Flavonoids exert their anti-atherogenic effects by increasing nitric oxide (NO), reducing reactive oxygen species (ROS), and decreasing pro-inflammatory cytokines. In addition, flavonoids alleviate ATI by decreasing triglyceride and cholesterol levels, as well as by attenuating inflammatory mediators. Furthermore, flavonoids inhibit synthesis of fatty acids and promote their oxidation. In this review, we discuss the effect of the main classes of flavonoids, namely flavones, flavonols, flavanols, flavanones, anthocyanins, and isoflavones, on atherosclerosis and ATI. In addition, we dissect the underlying molecular and cellular mechanisms of action for these flavonoids. We conclude by supporting the potential benefit for flavonoids in the management or treatment of CVD; yet, we call for more robust clinical studies for safety and pharmacokinetic values.


Assuntos
Tecido Adiposo/patologia , Aterosclerose/tratamento farmacológico , Flavonoides/uso terapêutico , Inflamação/tratamento farmacológico , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Aterosclerose/complicações , Flavonoides/química , Flavonoides/farmacologia , Humanos , Inflamação/complicações , Modelos Biológicos
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