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1.
Drug Discov Ther ; 14(2): 67-72, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32336723

RESUMO

The virus severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is currently affecting more than 200 countries and territories worldwide. It has been declared as pandemic by World Health Organization (WHO) and the whole world is suffering from corona virus disease 2019 (COVID-19). Currently, no treatment for SARS-CoV-2 are approved because of lack of evidence, but a number of clinical trials are in process and we are expecting fruitful results very soon. This review focuses on various approaches of treatment and few of the most recent clinical trials carried out in this field.


Assuntos
Antivirais/uso terapêutico , Infecções por Coronavirus/terapia , Pneumonia Viral/terapia , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Amidas/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Betacoronavirus , Cloroquina/uso terapêutico , Ensaios Clínicos como Assunto , Infecções por Coronavirus/tratamento farmacológico , Darunavir/uso terapêutico , Combinação de Medicamentos , Humanos , Hidroxicloroquina/uso terapêutico , Imunização Passiva , Indóis/uso terapêutico , Interferon-alfa/uso terapêutico , Interferon beta/uso terapêutico , Lopinavir/uso terapêutico , Pandemias , Pirazinas/uso terapêutico , Ritonavir/uso terapêutico
2.
Life Sci ; 250: 117602, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32240677

RESUMO

AIMS: Extrinsic ageing or photoageing relates to the onset of age-linked phenotypes such as skin hyperpigmentation due to UV exposure. UV induced upregulated production of tyrosinase enzyme, which catalyses the vital biochemical reactions of melanin synthesis is responsible for the inception of skin hyperpigmentation. We aimed to generate a validated QSAR model with a dataset consisting of 69 thio-semicarbazone derivatives to elucidate the physicochemical properties of compounds essential for tyrosinase inhibition and to identify novel lead molecules with enhanced tyrosinase inhibitory activity and bioavailability. MAIN METHODS: Lead optimization and insilico approaches were employed in this research work. QSAR model was generated and validated by exploiting Multiple Linear Regression method. Prioritization of lead-like compounds was accomplished by performing multi parameter optimization depleting molecular docking, bioavailability assessments and toxicity prediction for 69 compounds Derivatives of best lead compound were retrieved from chemical spaces. KEY FINDINGS: Molecular descriptors explicated the significance of chemical properties essential for chelation of copper ions present in the active site of tyrosinase protein target. Further, derivatives which comprise of electron donating groups in their chemical structure were predicted and analysed for tyrosinase inhibitory activity by employing insilico methodologies including chemical space exploration. SIGNIFICANCE: Our research work resulted in the generation of a validated QSAR model with higher degree of external predictive ability and significance to tyrosinase inhibitory activity. We propose 11 novel derivative compounds with enhanced tyrosinase inhibitory activity and bioavailability.


Assuntos
Química Farmacêutica/métodos , Biologia Computacional/métodos , Indóis/antagonistas & inibidores , Monofenol Mono-Oxigenase/antagonistas & inibidores , Pele/efeitos dos fármacos , Agaricales/metabolismo , Domínio Catalítico , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Elétrons , Inibidores Enzimáticos/farmacologia , Humanos , Ligação de Hidrogênio , Ligantes , Simulação de Acoplamento Molecular , Estrutura Molecular , Monofenol Mono-Oxigenase/metabolismo , Relação Quantitativa Estrutura-Atividade , Pigmentação da Pele/efeitos dos fármacos , Tiossemicarbazonas/química , Raios Ultravioleta
3.
Mutat Res ; 850-851: 503148, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32247557

RESUMO

Norharman exists in cigarette smoke and cooked foods and is non-mutagenic among Salmonella strains but mutagenic to S. typhimurium TA98 and YG1024 in the presence of S9 mix and aniline and o-toluidine. Co-mutagenesis of ß-carbolines and aniline and o-toluidine occurs through the formation of novel mutagenic aminophenyl-ß-carboline derivatives including 9-(4'-aminophenyl)-9H-pyrido[3,4-b]indole [aminophenylnorharman] (APNH)] and 9-(4'- amino-3'-methylphenyl)-9H-pyrido[3,4-b]indole [aminomethylphenylnorharman] (AMPNH)]. Since humans are often simultaneously exposed to ß-carbolines and aniline and o-toluidine, their effects on humans should be clarified. The most potent of these, APNH, induced both point mutations and small deletions in the liver and colon of gpt delta transgenic mice. Major APNH-induced mutations in the liver occurred at a G:C base pair, suggesting that APNH-DNA adducts (dG-C8-APNH) are potentially involved in these mutations. Furthermore, APNH induced hepatic and colon tumors harboring K-ras, ß-catenin, and Apc mutations in F344 rats, with high incidence. Mutations at G:C base pairs were predominant, similar to those in the in vivo mutation assay using gpt delta mice. Moreover, APNH detected in human urine samples obtained from both healthy volunteers on a normal diet and inpatients receiving parenteral alimentation; therefore, APNH can be considered an endogenous carcinogen contributing to tumorigenesis. Exposure levels of these aminophenyl-ß-carboline derivatives may be lower than those of carcinogenic heterocyclic amines (HCAs) including 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx); however, their health risks in terms of tumorigenesis may be comparable owing to stronger genotoxic effects of APNH rather than HCAs. This review summarized APNH mutagenicity/carcinogenicity, and its in vivo formation. Moreover, the effect on tumorigenesis in humans also discussed.


Assuntos
Carbolinas/química , Indóis/toxicidade , Mutagênese/efeitos dos fármacos , Piridinas/toxicidade , Toluidinas/química , Compostos de Anilina/toxicidade , Animais , Carbolinas/toxicidade , Colo/efeitos dos fármacos , Humanos , Fígado/efeitos dos fármacos , Camundongos , Camundongos Transgênicos , Mutação Puntual/efeitos dos fármacos , Toluidinas/toxicidade
4.
Drug Discov Ther ; 14(1): 58-60, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32147628

RESUMO

The SARS-CoV-2 virus emerged in December 2019 and then spread rapidly worldwide, particularly to China, Japan, and South Korea. Scientists are endeavoring to find antivirals specific to the virus. Several drugs such as chloroquine, arbidol, remdesivir, and favipiravir are currently undergoing clinical studies to test their efficacy and safety in the treatment of coronavirus disease 2019 (COVID-19) in China; some promising results have been achieved thus far. This article summarizes agents with potential efficacy against SARS-CoV-2.


Assuntos
Antivirais/farmacologia , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Descoberta de Drogas , Alanina/análogos & derivados , Alanina/farmacologia , Amidas/farmacologia , Antivirais/química , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/fisiologia , Cloroquina/farmacologia , Estudos Clínicos como Assunto , Humanos , Indóis/farmacologia , Pandemias , Pneumonia Viral , Pirazinas/farmacologia , Ribonucleotídeos/farmacologia , Replicação Viral/efeitos dos fármacos
5.
Biosci Trends ; 14(1): 64-68, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32037389

RESUMO

Pneumonia associated with the 2019 novel coronavirus (2019-nCoV) is continuously and rapidly circulating at present. No effective antiviral treatment has been verified thus far. We report here the clinical characteristics and therapeutic procedure for four patients with mild or severe 2019-nCoV pneumonia admitted to Shanghai Public Health Clinical Center. All the patients were given antiviral treatment including lopinavir/ritonavir (Kaletra®), arbidol, and Shufeng Jiedu Capsule (SFJDC, a traditional Chinese medicine) and other necessary support care. After treatment, three patients gained significant improvement in pneumonia associated symptoms, two of whom were confirmed 2019-nCoV negative and discharged, and one of whom was virus negative at the first test. The remaining patient with severe pneumonia had shown signs of improvement by the cutoff date for data collection. Results obtained in the current study may provide clues for treatment of 2019-nCoV pneumonia. The efficacy of antiviral treatment including lopinavir/ritonavir, arbidol, and SFJDC warrants further verification in future study.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Indóis/uso terapêutico , Lopinavir/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Ritonavir/uso terapêutico , Adulto , China , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
6.
Nat Commun ; 11(1): 855, 2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32071312

RESUMO

Cognitive decline is one of the complications of type 2 diabetes (T2D). Intermittent fasting (IF) is a promising dietary intervention for alleviating T2D symptoms, but its protective effect on diabetes-driven cognitive dysfunction remains elusive. Here, we find that a 28-day IF regimen for diabetic mice improves behavioral impairment via a microbiota-metabolites-brain axis: IF enhances mitochondrial biogenesis and energy metabolism gene expression in hippocampus, re-structures the gut microbiota, and improves microbial metabolites that are related to cognitive function. Moreover, strong connections are observed between IF affected genes, microbiota and metabolites, as assessed by integrative modelling. Removing gut microbiota with antibiotics partly abolishes the neuroprotective effects of IF. Administration of 3-indolepropionic acid, serotonin, short chain fatty acids or tauroursodeoxycholic acid shows a similar effect to IF in terms of improving cognitive function. Together, our study purports the microbiota-metabolites-brain axis as a mechanism that can enable therapeutic strategies against metabolism-implicated cognitive pathophysiologies.


Assuntos
Disfunção Cognitiva/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Jejum , Microbioma Gastrointestinal/fisiologia , Animais , Encéfalo/metabolismo , Cognição , Biologia Computacional , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2/complicações , Metabolismo Energético/genética , Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal/genética , Regulação da Expressão Gênica , Hipocampo/metabolismo , Indóis/metabolismo , Resistência à Insulina , Masculino , Metaboloma , Camundongos , Propionatos/metabolismo , RNA Ribossômico 16S , Serotonina/metabolismo , Sinapses/ultraestrutura , Ácido Tauroquenodesoxicólico/metabolismo
7.
Chemosphere ; 248: 125956, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32028156

RESUMO

Biofouling and organic fouling are major obstacles for polymeric membranes during application. In this work, zeolitic imidazolate framework-8@polydopamine (ZIF-8@PDA) nanoparticles were prepared by an aqueous synthesis strategy and incorporated into the polyamide (PA) selective layer to synthesize thin film nanocomposite membrane (TFN) during interfacial polymerization. The permeability and selectivity of the composite membrane were simultaneously improved with the introduction of ZIF-8@PDA. The water permeability of the TFN membrane increased to 3.74 ± 0.19 L/(m2·h·bar), which is 43.8% higher than that of the control membrane. Besides, the rejection of TFN membrane to sodium chloride is 98.68 ± 0.13%, which shows 0.99% increment than the unmodified membrane. Moreover, organic fouling and biofouling of the TFN membrane were also alleviated thanks to the introduction of the hydrophilic ZIF-8@PDA. The short-term filtration results indicate the performance of the TFN membrane is stable during operation.


Assuntos
Incrustação Biológica , Membranas Artificiais , Eliminação de Resíduos Líquidos/métodos , Purificação da Água/métodos , Filtração/métodos , Interações Hidrofóbicas e Hidrofílicas , Indóis , Nanocompostos , Nanopartículas , Nylons , Permeabilidade , Polímeros , Água , Zeolitas
9.
J Photochem Photobiol B ; 204: 111808, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32006892

RESUMO

Photodynamic therapy (PDT) is effective in the treatment of different types of cancer, such as basal cell carcinoma and other superficial cancers. However, improvements in photosensitizer delivery are still needed, and the use of PDT against more deeply located tumors has been the subject of many studies. Thus, the goal of this study was to evaluate the efficacy of a nanoemulsion containing aluminium-phthalocyanine (AlPc-NE) as a mediator of photodynamic therapy (PDT-AlPc-NE) against grafted 4T1 breast adenocarcinoma tumors in mice (BALB/c). Short after the appearance of the tumor, the animals were divided into groups (n = 5) as follows: untreated; only AlPc-NE and treated with PDT-AlPc-NE. The tumor volume was measured with a digital calliper at specific times. The presence of metastasis in the lungs was evaluated by microtomography and histopathological analyses. The results show that the application of PDT-AlPc-NE eradicated the transplanted tumors in all the treated animals, while the animals from control groups presented a robust increase in the tumor volume. Still more significantly, microtomography showed the animals submitted the PDT-AlPc-NE to be free of detectable metastasis in the lungs. The histological analysis of the lungs further confirmed the results verified by the microtomography. Therefore, this study suggests that PDT-AlPc-NE is effective in the elimination of experimentally grafted breast tumors in mice and also in preventing the formation of metastasis in the lungs.


Assuntos
Adenocarcinoma/tratamento farmacológico , Alumínio/química , Neoplasias da Mama/tratamento farmacológico , Indóis/química , Neoplasias Pulmonares/tratamento farmacológico , Nanoestruturas/química , Fármacos Fotossensibilizantes/uso terapêutico , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Animais , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Endogâmicos BALB C , Nanoestruturas/uso terapêutico , Nanoestruturas/toxicidade , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Transplante Homólogo , Microtomografia por Raio-X
10.
J Photochem Photobiol B ; 204: 111811, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32028187

RESUMO

The development of multidrug resistance is often associated with the over-expression of P-glycoprotein (P-gp). This protein prevents drug accumulation and extrudes them out of the cell before they reach the intended target. The aim of this study was to develop an in vitro MCF-7 cell line with increased expression of P-gp and test the phototoxicity of a novel photoactivated zinc phthalocyanine tetrasulfonic acid (ZnPcS4) on these cells. The over-expressed P-gp MCF-7 cells (MCF-7/DOX) were developed from wildtype (WT) MCF-7 cells by a stepwise continuous exposure of the WT cells to different concentrations of Doxorubicin (DOX) (0.1 - 1 µM) over a period of 4 months. The P-gp expression was measured using flow cytometry, immunofluorescence and enzyme immunoassay. To verify whether zinc phthalocyanine-mediated photodynamic therapy (ZnPcS4 - PDT) is effective in MCF-7/DOX, we studied the subcellular localization, phototoxicity and nuclear damage. The flow cytometry result showed two distinct peaks of P-gp positive and negative expression in MCF-7/DOX cell population, which correlates with the ELISA-based assay (p˂0.001). The ME16C (Normal breast cells) was used as control. The localization studies showed that ZnPcS4 have greater affinity for lysosome than mitochondria. Phototoxicity results indicated that photoactivated zinc phthalocyanine decreased the cell proliferation and viability as the drug and laser light dosages increased to 16 µM and 20 J/cm2 respectively. PDT-induced cytotoxicity using lactose dehydrogenase (LDH) enzyme leakage as measure did not increase likewise. The ZnPcS4-induced PDT was less effective for MCF-7/DOX cells which could be attributed to decreased retention of ZnPcS4 in major cellular organelles due to the presence of increased drug efflux P-gp. The current findings suggest that, increased P-gp expression, a characteristic of multidrug resistance together with other related intrinsic mechanisms might contribute to render MCF-7/DOX cells less sensitive to ZnPcS4-induced phototoxicity.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Proliferação de Células/efeitos dos fármacos , Indóis/farmacologia , Lasers Semicondutores , Compostos Organometálicos/farmacologia , Trifosfato de Adenosina/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos da radiação , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos da radiação , Feminino , Humanos , Indóis/química , Células MCF-7 , Compostos Organometálicos/química , Fotoquimioterapia , Rodamina 123/química , Rodamina 123/metabolismo
11.
Artigo em Chinês | MEDLINE | ID: mdl-32062902

RESUMO

Pulmonary fibrosis is the terminal manifestation of a variety of interstitial lung diseases. Idiopathic pulmonary fibrosis (IPF) is one of the chronic, progressive, fibrotic lung disease with high incidence and poor prognosis. Nintedanib and pirfenidone are currently marketed anti-pulmonary fibrosis drugs, and their efficacy and safety are recognized in patients with IPF. This article reviews the targets and clinical trials of the two drugs, and provides a basis for the expansion of indications for anti-pulmonary fibrosis drugs.


Assuntos
Indóis/farmacologia , Piridonas/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos
12.
Int J Nanomedicine ; 15: 137-149, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32021170

RESUMO

Purpose: Traditional chemotherapy is accompanied by significant side effects, which, in many aspects, limits its treatment efficacy and clinical applications. Herein, we report an oxidative responsive polymersome nanosystem mediated by near infrared (NIR) light which exhibited the combination effect of photodynamic therapy (PDT) and chemotherapy. Methods: In our study, poly (propylene sulfide)20-bl-poly (ethylene glycol)12 (PPS20-b-PEG12) block copolymer was synthesized and employed to prepare the polymersome. The hydrophobic photosensitizer zinc phthalocyanine (ZnPc) was loaded in the shell and the hydrophilic doxorubicin hydrochloride (DOX·HCl) in the inner aqueous space of the polymersome. Results: Under the irradiation of 660 nm NIR light, singlet oxygen 1O2 molecules were generated from ZnPc to oxidize the neighbouring sulfur atoms on the PPS block which eventually ruptured the intact structure of polymersomes, leading to the release of encapsulated DOX·HCl. The released DOX and the 1O2 could achieve a combination effect for cancer therapy if the laser activation and drug release occur at the tumoral sites. In vitro studies confirmed the generation of singlet oxygen and DOX release by NIR irradiation. In vivo studies showed that such a combined PDT-chemotherapy nanosystem could accumulate in A375 tumors efficiently, thus leading to significant inhibition on tumor growth as compared to PDT (PZ group) or chemotherapy alone (DOX group). Conclusion: In summary, this oxidation-sensitive nanosystem showed excellent anti-tumor effects by synergistic chemophotodynamic therapy, indicating that this novel drug delivery strategy could potentially provide a new means for cancer treatments in clinic.


Assuntos
Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Melanoma Experimental/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Doxorrubicina/farmacocinética , Liberação Controlada de Fármacos , Humanos , Indóis/administração & dosagem , Indóis/química , Lasers , Masculino , Camundongos Endogâmicos BALB C , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/química , Fármacos Fotossensibilizantes/química , Polietilenoglicóis/química , Polímeros/química , Oxigênio Singlete/farmacocinética , Sulfetos/química
13.
Int J Nanomedicine ; 15: 301-313, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32021181

RESUMO

Purpose: Multifunctional drug delivery systems (DDS) are emerging as a new strategy to highly treat malignant tumors. The aim of this study is to develop a drug dual-carriers delivery system (DDDS) using the natural protein ferritin (FRT) and a nanoscale graphene oxide (NGO) as dual-carriers. Methods: The FRT is a pH-sensitive hollow cage protein with disassembly and reassembly properties and the NGO has a large surface area and a photothermal effect by which it can load and release drugs under near-infrared irradiation (NIR). Due to these unique features, the NGO loaded the anticancer drug resveratrol (RSV) and the conjugated mitochondrion targeted molecule IR780 as IR780-NGO-RSV (INR), the first drug delivery platform. Next, the INR was capsulated by FRT to form the DDDS INR@FRT which was applied for synergistic photothermal-chemotherapy of ovarian cancer. Results: Through a series of characterizations, INR@FRT showed a uniform nanosphere structure and remarkable stability in physiological condition. Heat/pH 5.0 was confirmed to trigger RSV release from the INR@FRT. After taken up by cells, INR@FRT located to the lysosomes where the acidic environment triggered INR release. INR targeted the mitochondrion and released RSV to directly react with organelles, which in turn decreased the mitochondrion membrane potential and caused cell apoptosis. In-vivo experiments showed that INR@FRT combined with NIR irradiation displayed remarkable tumor suppression with a high survival rate after 60 days of treatment. Finally, the biocompatibility of INR@FRT was demonstrated in vitro and in vivo. Conclusion: These results highlight the immense potential of INR@FRT as a type of DDDS for the treatment of tumors.


Assuntos
Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Indóis/farmacologia , Mitocôndrias/efeitos dos fármacos , Nanoestruturas/química , Neoplasias Ovarianas/tratamento farmacológico , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Liberação Controlada de Fármacos , Feminino , Ferritinas/química , Grafite/química , Temperatura Alta , Humanos , Concentração de Íons de Hidrogênio , Indóis/administração & dosagem , Indóis/química , Raios Infravermelhos , Camundongos Nus , Nanoestruturas/administração & dosagem , Resveratrol/administração & dosagem , Resveratrol/farmacocinética , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Top Curr Chem (Cham) ; 378(2): 22, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32030596

RESUMO

Heterocyclic compounds having a nitrogen atom in the ring exhibit very interesting biological activities. Indole is the core structure of many bioactive compounds owing to its high affinity to bind with most biological targets. Indole is an electron-rich compound and generally prefers electrophilic rather than nucleophilic substitution. Hence, many important indole derivatives are difficult to synthesize through the conventional reactivity of indole. This limitation can be avoided by using the umpolung, from the German word meaning polarity inversion. In umpolung, the indole molecule, especially the C2 and C3 positions, behave as an electrophile. As C2-functionalized indoles have substantial importance in synthetic and pharmaceutical chemistry, this review focuses on the C2 umpolung of indoles via the indirect approach which is less explored. Unlike direct approaches of indole umpolung, indirect methods have several advantages and therefore a number of research articles have been published in this field. But no review is available up till now. This is the first review on this topic and we believe that it will surely motivate the readers to work in this area further.


Assuntos
Carbono/química , Indóis/química , Alcaloides/síntese química , Alcaloides/química , Catálise , Ciclização , Iodo/química , Quinolinas/síntese química , Quinolinas/química , Ácidos Sulfínicos/química
15.
Chem Commun (Camb) ; 56(20): 3089-3092, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32052805

RESUMO

Reaction of FeIII(O2˙-)(TPP) with 2,3-dimethylindole at -40 °C gives the ring-opened, dioxygenated N-(2-acetyl-phenyl)-acetamide product. The reaction was monitored in situ by low-temperature UV-vis and 1H NMR spectroscopies. This work demonstrates that a discrete iron(iii)(superoxo) porphyrin is competent to carry out indole oxidation, as proposed for the tryptophan and indoleamine 2,3-dioxygenases.


Assuntos
Compostos Férricos/química , Indolamina-Pirrol 2,3,-Dioxigenase/química , Indóis/química , Metaloporfirinas/química , Superóxidos/química , Triptofano Oxigenase/química , Compostos Férricos/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Indóis/metabolismo , Metaloporfirinas/metabolismo , Estrutura Molecular , Oxirredução , Superóxidos/metabolismo , Triptofano Oxigenase/metabolismo
16.
J Agric Food Chem ; 68(9): 2795-2802, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32031786

RESUMO

Polydopamine (PDA) possesses high aqueous dispersibility, strong optical absorption, and a zwitterionic property, which give it multitudes of advantages to coat light-sensitive hydrophobic curcumin (Cur) for pH-responsive release. However, PDA is formed in alkaline conditions, which hinders its potential application for alkali-sensitive curcumin coating. Here, we developed a method to prepare PDA-coated Cur nanoparticles (NPs), which reduced chemical degradation of Cur in alkaline conditions. Encapsulation efficiency and loading capacity decreased to 73.69% and 51.80%, as the time for dopamine polymerization went on. PDA could protect Cur from light-induced degradation in powder and solution forms. Controlled release and pH-responsive delivery of PDA-coated Cur were observed under stomach and intestinal conditions compared to free Cur, which resulted from the coverage and thickness of the PDA shell and the electrostatic attraction between PDA and Cur. PDA-coated Cur NPs could be a promising way for the application of Cur in the beverage and food industry.


Assuntos
Curcumina/química , Indóis/química , Nanopartículas/química , Polímeros/química , Portadores de Fármacos/química , Composição de Medicamentos , Concentração de Íons de Hidrogênio , Cinética , Tamanho da Partícula
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