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1.
Water Environ Res ; 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31650659

RESUMO

A p-type TiO2 with Ti vacancies (D-TiO2 ) was synthesized by a facile solvothermal treatment, and Ag/TiO2 with different Ag loading amount was prepared through a photo-reduction deposition method. The samples were characterized through scanning electron microscopy, transmission electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. The adsorption and photocatalytic characteristics of tetrabromobisphenol A (TBBPA) on D-TiO2 and Ag/TiO2 were investigated. The adsorption of TBBPA on Ag/TiO2 was significantly enhanced and was five times greater than that of pure TiO2 . The increase in pH significantly inhibited the adsorption of TBBPA. The 2%-Ag/TiO2 nearly completely degraded TBBPA in 10 min under UV-Vis light (λ > 360 nm), and the apparent reaction rate constant (kapp ) reached 0.63 min-1 . The significantly enhanced UV-Vis light catalytic properties of the Ag/TiO2 in comparison with that of TiO2 were attributed to the increased adsorption capacity and electron transfer ability of the Ag/TiO2 . Free radical trap experiments results showed that holes and superoxide radicals play a major role in the catalytic degradation of TBBPA by Ag/TiO2 . Moreover, the Ag/TiO2 catalyst exhibits high stability during TBBPA degradation even after three cycles. PRACTITIONER POINTS: Ti-defected TiO2 and Ag/TiO2 were synthesized using a solvothermal and photo-reduction deposition, respectively. Ag/TiO2 exhibited outstanding adsorption and photocatalytic activity for TBBPA removal under UV-Vis light. Holes and superoxide radicals play a major role in the photocatalytic degradation of TBBPA.

2.
J Med Chem ; 62(17): 7941-7960, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31403780

RESUMO

A series of substituted 4,6-dihydrospiro[[1,2,3]triazolo[4,5-b]pyridine-7,3'-indoline]-2',5(3H)-dione analogues were synthesized and evaluated as potent dengue virus inhibitors. Throughout a structure-activity relationship exploration on the amide of the indolone moiety, a wide range of substitutions were found to be well tolerated for chemical optimization at this position. Among these compounds, 15 (JMX0254) displayed the most potent and broad inhibitory activities, effective against DENV-1 to -3 with EC50 values of 0.78, 0.16, and 0.035 µM, respectively, while compounds 16, 21, 27-29, 47, and 70 exhibited relatively moderate to high activities with low micromolar to nanomolar potency against all four serotypes. The biotinylated compound 73 enriched NS4B protein from cell lysates in pull-down studies, and the findings together with the mutation investigations further validated dengue NS4B protein as the target of this class of compounds. More importantly, compound 15 exhibited good in vivo pharmacokinetic properties and efficacy in the A129 mouse model, indicating its therapeutic potential against the dengue virus infection as a drug candidate for further preclinical development.

3.
Tuberculosis (Edinb) ; 116S: S28-S33, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31080089

RESUMO

The human immunodeficiency virus (HIV) pandemic is driving the re-emergence of tuberculosis (TB) as a global health threat, both by increasing the susceptibility of HIV-infected people to infection with Mycobacterium tuberculosis (Mtb), and increasing the rate of emergence of drug-resistant Mtb. There are several other clinical challenges for treatment of co-infected patients including: expense, pill burden, toxicity, and malabsorption that further necessitate the search for new drugs that may be effective against both pathogens simultaneously. The anti-helminthic niclosamide has been shown to have activity against a laboratory strain of Mtb in liquid culture while bacteriostatic activity against non-replicating M. abscessus was also recently described. Here we extend these findings to further demonstrate that niclosamide inhibits mycobacterial growth in infected human macrophages and mediates potent bacteriostatic activity against the virulent Mtb Beijing strain. Importantly, we provide the first evidence that niclosamide inhibits HIV replication in human macrophages and Jurkat T cells through post-integration effects on pro-virus transcription. The dual antiviral and anti-mycobacterial activity was further observed in an in vitro model of HIV and Mtb co-infection using human primary monocyte-derived macrophages. These results support further investigation of niclosamide and derivatives as anti-retroviral/anti-mycobacterial agents that may reduce clinical challenges associated with multi-drug regimens and drug resistance.


Assuntos
Fármacos Anti-HIV/farmacologia , Antituberculosos/farmacologia , HIV-1/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Niclosamida/farmacologia , Linfócitos T/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Coinfecção , HIV-1/crescimento & desenvolvimento , Humanos , Células Jurkat , Macrófagos/microbiologia , Macrófagos/virologia , Mycobacterium tuberculosis/crescimento & desenvolvimento , Mycobacterium tuberculosis/patogenicidade , Linfócitos T/virologia , Virulência
4.
Bioorg Med Chem Lett ; 29(11): 1399-1402, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30954430

RESUMO

Carbapenemase-producing Enterobacteriaceae (CPE) represents the most worrisome evolution of the antibiotic resistance crisis, which is almost resistant to most of available antibiotics. This situation is getting even worse particularly due to the recent emergence of colistin resistance. Herein, niclosamide, an FDA-approved traditional drug, and its novel O-alkylamino-tethered derivatives were discovered as new and potent antibacterial agents against carbapenemase-producing and/or colistin resistant Enterobacteriaceae isolates. Among these molecules, compound 10 (HJC0431) with 4-aminobutyl moiety showed the broad antibacterial activities, effective against 6 strains. In vitro checkerboard and time-kill course studies demonstrated the synergistic effects of the screened compounds with colistin against the corresponding strains with various degrees.

5.
J Surg Res ; 232: 283-292, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30463731

RESUMO

BACKGROUND: Liver fibrosis is characterized as excessive deposition of the extracellular matrix proteins, primarily by activated hepatic stellate cells (HSCs). NF-κB has been reported as one of the major mediators of HSC activation. Previously, our team reported that oridonin exhibited antihepatic fibrogenetic activity in vitro. In this study, we examined the effects of its novel derivative CYD0618 on HSC viability, apoptosis, and NF-κB signaling. METHODS: Cell proliferation of activated human and rat HSC lines LX-2 and HSC-T6 was measured using Alamar Blue Assay. Apoptosis was measured by a Cell Death Detection ELISA kit. Cellular proteins were determined by Western blots and immunofluorescence. RESULTS: CYD0618 significantly inhibited LX-2 and HSC-T6 cell proliferation in a dose-dependent manner. CYD0618 induced cell apoptosis in both cell lines. CYD0618 treatment increased cell cycle inhibitory protein p21, p27, and induced apoptosis marker cleaved poly (ADP-ribose) polymerase, while suppressing the expression of Collagen type 1. CYD0618 blocked lipopolysaccharide (LPS)-induced NF-κB p65 nuclear translocation and DNA binding activity and prevented LPS-induced NF-κB inhibitory protein IκBα phosphorylation and degradation. LPS-stimulated NF-κB downstream target cytokines IL-6 and MCP-1 were attenuated by CYD0618. Endogenous and LPS-stimulated NF-κB p65 S536 phosphorylation was inhibited by CYD0618 treatment. CONCLUSIONS: The potent antihepatic fibrogenetic effect of CYD0618 may be mediated via suppression of the NF-κB pathway.


Assuntos
Diterpenos de Caurano/farmacologia , Cirrose Hepática/tratamento farmacológico , NF-kappa B/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Colágeno Tipo I/análise , Células Estreladas do Fígado/efeitos dos fármacos , Humanos , NF-kappa B/fisiologia , Nitrilos/farmacologia , Ratos , Sulfonas/farmacologia
6.
Molecules ; 23(2)2018 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-29470395

RESUMO

Oridonin, a diterpenoid natural product commonly used in East Asian herbal medicine, is garnering increased attention in the biomedical community due to its extensive biological activities that include antitumor, anti-inflammatory, antimicrobial, hepatic fibrosis prevention, and neurological effects. Over the past decade, significant progress has been made in structure activity relationship and mechanism of action studies of oridonin for the treatment of cancer and other diseases. This review provides a brief summary on oridonin and its analogs in cancer drug discovery and antiinflammation and highlights its emerging therapeutic potential in neuroprotection applications.


Assuntos
Diterpenos de Caurano/uso terapêutico , Inflamação/tratamento farmacológico , Neoplasias/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Diterpenos de Caurano/química , Humanos , Fármacos Neuroprotetores/química , Relação Estrutura-Atividade
8.
Zhongguo Zhen Jiu ; 37(9): 913-7, 2017 Sep 12.
Artigo em Chinês | MEDLINE | ID: mdl-29354909

RESUMO

OBJECTIVE: To observe the impacts on post-stroke unilateral spatial neglect treated with acupuncture for "regaining consciousness, benefiting marrow and opening orifices" and rehabilitation. METHODS: Forty patients of post-stroke unilateral spatial neglect were randomized into an observation group and a control group, 20 cases in each one. In the observation group, acupuncture was applied to the acupoints for "regaining consciousness, benefiting marrow and opening orifices", named Baihui (GV 20), Sishencong (EX-HN 1), Benshen (GB 13), Shenting (GV 24), and the bilateral yuan-primary points and luo-connecting points of the heart meridian, pericardium meridian and kidney meridian, as well as the acupoints along the affected meridians. Additionally, the rehabilitation was provided. In the control group, acupuncture at the acupoints along the affected meridians and rehabilitation were adopted. The treatment was given once a day, 5 times a week. After 8 weeks of treatment the evaluation was made. the indexes of unilateral spatial neglect such as line bisection test, the score of the mini-mental state examination (MMSE), the score of simple Fugl-Meyer motor function assessment and the modified Barthel indexes were adopted for the assessment of the severity of unilateral spatial neglect, cognitive function, motor function, and the activities of daily living. RESULTS: After treatment, the indexes of unilateral spatial neglect (line bisection test, line cancellation test, clock-drawing test and copying drawing test), MMSE score, the simple Fugl-Meyer motor function assessment and modified Barthel indexes were all improved as compared with those before treatment in the two groups (all P<0.01). The improvements in the observation group were more obvious than those in the control group (P<0.05, P<0.01). CONCLUSION: The combination of acupuncture treatment for "regaining consciousness, benefiting marrow and opening orifices" and rehabilitation much more effectively alleviates the severity of post-stroke unilateral spatial neglect and improves the motor function and the activities of daily living in the patients.


Assuntos
Pontos de Acupuntura , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/psicologia , Atividades Cotidianas , Terapia por Acupuntura/métodos , Humanos , Rim , Meridianos , Testes Neuropsicológicos , Pericárdio , Comportamento Espacial , Resultado do Tratamento
9.
Biotechnol Biofuels ; 9: 36, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26877766

RESUMO

BACKGROUND: Cellulose, an abundant and renewable polysaccharides, constitutes the largest resource for bioconversion of biofuels. Plant polysaccharides hydrolysis is catalyzed by cellulases, which include endoglucanases, exoglucanases, and ß-glucosidases. Converting cellulose and hemicellulose to short chains of oligosaccharides by endo-/exoglucanases is the key step for biofuel transformation. Intriguingly, ß-glucanases with transglycosylation activity not only can relieve product inhibition of glucan hydrolysis but also has potential application as biocatalysts for functional materials. RESULTS: Here, a metagenomic fosmid library was constructed from a paddy soil for cellulase screening. One purified clone showing carboxymethylcellulase activity was isolated, and the complete ß-glucanase gene (umcel9y-1) was cloned and overexpressed in Escherichia coli. Phylogenetic analysis indicated that ß-glucanase Umcel9y-1 belonged to the theme C of glycoside hydrolase family 9. Amino acids sequence showed 58.4 % similarity between Umcel9y-1 and its closest characterized reference, cellulase Cel01. Biological characterization showed that Umcel9y-1 was an efficient endoglucanase and also exhibited high activities of exoglucanase and transglycosylation. The transglycosylation products of Umcel9y-1 including sophorose, laminaribiose, and gentiobiose, and transglycosylation was detected under all activated conditions. The order of catalytic efficiency for polysaccharides, cellooligosaccharides, and aryl-ß-glycosides was p-nitrophenol-D-cellobioside, barley glucan, cellopentaose, cellotetraose, cellotriose, hydroxyethylcellulose, cellohexose, laminarin, and carboxymethylcellulose, respectively. The barley glucan was the optimal polysaccharides for Umcel9y-1 with K m and K cat/K m values of 13.700 mM and 239.152 s(-1) mM(-1), respectively. CONCLUSION: Biological characterizations of recombinant Umcel9y-1 showed that the versatile ß-glucanase had efficient endoglucanase activity to barley glucan and also exhibited high activities of exoglucanase and transglycosylation. The optimum conditions of recombinant Umcel9y-1 was pH 6.5-7.0 at 37 °C with predominant halotolerance and high-thermal stability. These results indicate that the novel metagenomic-derived ß-glucanase may be a potent candidate for industrial applications.

11.
Chin Med J (Engl) ; 127(21): 3700-5, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25382322

RESUMO

BACKGROUND: Myocarditis is a common, potentially life-threatening disease that presents a wide rang of symptoms in children, as an important underlying etiology of other myocardial diseases such as dilated and arrhythmogenic right ventricular cardiomyopathy. The incidence of nonfatal myocarditis is probably greater than that of the one actually diagnosed, which is the result of the challenges of establishing the diagnosis in standard clinical settings. Currently, no single clinical or imaging finding confirms the diagnosis of myocarditis with absolute certainty. Historically, clinical exam, electrocardiogram (ECG), serology and echocardiography had an unsatisfactory diagnostic accuracy in myocarditis. Endomyocardial biopsy remains as a widely accepted standard, but may not be suitable for every patient, especially for those with less severe disease. Our aim was to find the changes in cardiovascular magnetic resonance (CMR) imaging of children with myocarditis diagnosed by clinical criteria. METHODS: We studied 25 children (18 male, 7 female; aged from 5-17 years) with diagnosed myocarditis by clinical criteria. CMR included function analyses, T2-weighted imaging, T1-weighted imaging before and after i.v. gadolinium injection (early gadolinium enhancement (EGE) and late gadolinium enhancement (LGE)). RESULTS: The T2 ratio was elevated in 21 children (84%, 11 in anterolateral (44%), 5 in inferolateral (20%), and 5 in septum (20%)), EGE was present in 9 children (36%, 3 in anterolateral (12%), 4 in inferolateral (20%), and 2 in septum (8%)), and LGE was present in 5 children (20%, 2 in anterolateral (8%), 1 in inferolateral (4%), 1 in septum (4%), and 1 in midwall of left ventricular (LV) wall). In 9 children (36%), two (or more) out of three sequences (T2, EGE, LGE) were abnormal. CONCLUSIONS: The CMR findings in children with clinically diagnosed myocarditis vary within the groups, including regional or global myocardial signal increase in T2-weighted images, EGE and LGE in T1-weighted images. The T2 ratio elevation is the most common CMR finding. Children with mild cardiac symptoms may also appear serious myocardial injuries.


Assuntos
Imagem por Ressonância Magnética/métodos , Miocardite/patologia , Miocárdio/patologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino
12.
Org Biomol Chem ; 12(22): 3721-34, 2014 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-24781551

RESUMO

A library of biscoumarin-based c-Met inhibitors was synthesized, based on optimization of 3,3'-biscoumarin hit 3, which was identified as a non-ATP competitive inhibitor of c-Met from a diverse library of coumarin derivatives. Among these compounds, 38 and 40 not only showed potent enzyme activities with IC50 values of 107 nM and 30 nM, respectively, but also inhibited c-Met phosphorylation in BaF3/TPR-Met and EBC-1 cells.


Assuntos
Cumarínicos/síntese química , Cumarínicos/farmacologia , Desenho de Drogas , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Trifosfato de Adenosina/farmacologia , Cumarínicos/química , Humanos , Concentração Inibidora 50 , Inibidores de Proteínas Quinases/química , Umbeliferonas/síntese química , Umbeliferonas/química , Umbeliferonas/farmacologia
14.
Zhen Ci Yan Jiu ; 37(4): 308-11, 2012 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-23140053

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Zusanli" (ST 36)-"Quchi" (LI 11) on behavior changes and spinal inflammatory reactions in spinal ischemia-reperfusion injury (SI/RI) rabbits, so as to assess its protective effect on SI/RI. METHODS: Thirty New Zealand rabbits were randomly divided into sham-operation (sham), SI/RI model (model) and EA groups. SI/RI model was established by occlusion of the abdominal aorta for 45 min. EA (2 Hz, 1 mA) was applied to bilateral "Zusanli" (ST 36)-"Quchi" (LI 11) for 30 min after modeling, 4 times (0 h, 12 h, 24 h and 36 h after modeling) altogether. The animals' motor function score of the hindlimb was assessed according to Tarlov's method. The contents of tumor necrosis factor-alpha (TNF-alpha) and Interleukin-6 (IL-6) of the lumbar spinal cord tissue were assayed by ELISA 48 h after modeling. RESULTS: Compared with the sham group, the animals' motor scores at 24 h and 48 h after modeling were decreased, and spinal TNF-alpha and IL-6 contents were increased significantly (all P < 0.05) in the model group. In comparison with the model group, the animals' motor scores at both 24 h and 48 h were up-regulated considerably in the EA group (P < 0.05), suggesting an improvement of the neuronal function after EA intervention. The spinal TNF-alpha and IL-6 contents were obviously lower in the EA group than in the model group (P < 0.05). CONCLUSION: Electroacupuncture has a protective effect on the spinal cord ischemia- reperfusion injury of rabbits probably by reducing the local inflammatory reactions.


Assuntos
Eletroacupuntura , Interleucina-6/metabolismo , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/terapia , Isquemia do Cordão Espinal/cirurgia , Fator de Necrose Tumoral alfa/metabolismo , Animais , Humanos , Interleucina-6/genética , Masculino , Coelhos , Reperfusão/efeitos adversos , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/genética , Medula Espinal/metabolismo , Fator de Necrose Tumoral alfa/genética
15.
J Bacteriol ; 194(10): 2458-69, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22389479

RESUMO

Synthesis of the Fis nucleoid protein rapidly increases in response to nutrient upshifts, and Fis is one of the most abundant DNA binding proteins in Escherichia coli under nutrient-rich growth conditions. Previous work has shown that control of Fis synthesis occurs at transcription initiation of the dusB-fis operon. We show here that while translation of the dihydrouridine synthase gene dusB is low, unusual mechanisms operate to enable robust translation of fis. At least two RNA sequence elements located within the dusB coding region are responsible for high fis translation. The most important is an AU element centered 35 nucleotides (nt) upstream of the fis AUG, which may function as a binding site for ribosomal protein S1. In addition, a 44-nt segment located upstream of the AU element and predicted to form a stem-loop secondary structure plays a prominent role in enhancing fis translation. On the other hand, mutations close to the AUG, including over a potential Shine-Dalgarno sequence, have little effect on Fis protein levels. The AU element and stem-loop regions are phylogenetically conserved within dusB-fis operons of representative enteric bacteria.


Assuntos
Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Fator Proteico para Inversão de Estimulação/metabolismo , Regulação Bacteriana da Expressão Gênica/fisiologia , RNA Bacteriano/metabolismo , Sequência de Bases , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Fator Proteico para Inversão de Estimulação/genética , Mutação , Conformação de Ácido Nucleico , Óperon , Ligação Proteica , Biossíntese de Proteínas , RNA Bacteriano/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
16.
Biochem Biophys Res Commun ; 415(4): 591-6, 2011 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-22074822

RESUMO

Geometric features such as size and shape of the microenvironment are known to alter cell behaviors such as growth, differentiation, apoptosis, and migration. Little is known, however, about the effect of curvature on cell behaviors despite that many cells reside in curved space of tubular organs such as the bronchial airways. To address this question, we fabricated micropatterned strips that mimic airway walls with varying curvature. Then, we cultured airway smooth muscle cells (ASMCs) on these strips and investigated the cells' motility and mechanical properties using time-lapse imaging microscopy and optical magnetic twisting cytometry (OMTC). We found that both motility and mechanical properties of the ASMCs were influenced by the curvature. In particular, when the curvature increased from 0 to 1/150 µm(-1), the velocity of cell migration first decreased (0-1/750 µm(-1)), and then increased (1/750-1/150 µm(-1)). In contrast, the cell stiffness increased and then decreased. Thus, at the intermediate curvature (1/750 µm(-1)) the ASMCs were the least motile, but most stiff. The contractility instead decreased consistently as the curvature increased. The level of F-actin, and vinculin expression within the ASMCs appeared to correlate with the contractility and motility, respectively, in relation to the curvature. These results may provide valuable insights to understanding the heterogeneity of airway constrictions in asthma as well as the developing and functioning of other tubular organs and tissue engineering.


Assuntos
Movimento Celular , Forma Celular , Miócitos de Músculo Liso/fisiologia , Traqueia/citologia , Animais , Células Cultivadas , Citoesqueleto/ultraestrutura , Fenômenos Mecânicos , Miócitos de Músculo Liso/citologia , Ratos , Ratos Sprague-Dawley
17.
Zhongguo Zhong Yao Za Zhi ; 36(2): 112-6, 2011 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-21506404

RESUMO

In order to clarify original plants of traditional Chinese medicine (TCM) frankincense, a GC method for determination essential oils and a HPLC method for determination boswellic acids were carried out together with analysis of herbalism, botany, components and pharmacology papers of frankincense. It was concluded that original plants of TCM frankincense include at least Boswellia sacra, B. papyrifera and B. serrata.


Assuntos
Boswellia/química , Medicina Herbária , Extratos Vegetais/análise , Boswellia/classificação , Cromatografia Líquida de Alta Pressão
18.
J Org Chem ; 76(8): 2694-700, 2011 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-21391709

RESUMO

Total synthesis of tropane alkaloids (-)-cocaine and (-)-ferruginine were accomplished in nine steps each and in 55% and 46% overall yields, respectively, starting from the known Betti base derivative (+)-(7aR,10R,12S)-10-(1H-benzotriazol-1-yl)-7a,8,9,10-tetrahydro-12-phenyl-12H-naphtho[1,2-e]pyrrolo[2,1-b][1,3]oxazine. In this novel route, RCM reaction and 1,3-dipolar cycloaddition were employed as key steps for the enantioselective construction of tropane skeleton and the regioselective introduction of 3-bromo-2-isoxazoline ring as masked cis-2,3-disubstituents. To obtain the desired precursor (2S,5R)-2-allyl-5-vinylpyrrolidine for RCM reaction, we developed a general and practical method for the preparation of enantiopure cis-2,5-disubstituted pyrrolidines bearing alkene- and/or alkyne-containing substituents. We also offered two highly efficient pathways for the conversion of the 3-bromo-2-isoxazoline ring into the desired cis-2,3-disubstituted groups in (-)-cocaine and (-)-ferruginine.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/síntese química , Cocaína/síntese química , Agonistas Nicotínicos/síntese química , Pirrolidinas/síntese química , Alcenos/química , Alquinos/química , Compostos Bicíclicos Heterocíclicos com Pontes/metabolismo , Cocaína/metabolismo , Inibidores da Captação de Dopamina/antagonistas & inibidores , Inibidores da Captação de Dopamina/metabolismo , Estrutura Molecular , Agonistas Nicotínicos/metabolismo , Receptores Dopaminérgicos/metabolismo , Receptores Nicotínicos/metabolismo , Estereoisomerismo , Compostos de Vinila/química
19.
J Org Chem ; 76(1): 188-94, 2011 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-21121617

RESUMO

Total synthesis of (+)-epilupinine was accomplished in nine steps and in 48% overall yield, in which INOC was used as the key step for the construction of the quinolizidine skeleton. We found that it was an extremely difficult task to prepare the key intermediates (R)-N-(3-nitropropyl)-2-vinylpiperidine or (R)-(2-vinylpiperid-1-yl)propanal by routine methods. Thus, by using Fukuyama's oxime synthesis, a general method was developed for highly efficient conversion of 3-(N,N-dialkylamino)propanols into 3-(N,N-dialkylamino)propanal oximes without using the corresponding aldehydes.


Assuntos
Cicloparafinas/química , Nitrilos/química , Óxidos/química , Esparteína/análogos & derivados , Ciclização , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Esparteína/síntese química , Esparteína/química , Estereoisomerismo
20.
Zhongguo Zhen Jiu ; 30(7): 537-41, 2010 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-20862933

RESUMO

OBJECTIVE: To observe the effect of acupuncture combined with speech therapy for dysarthria after stroke or cerebral trauma. METHODS: Sixty-one cases were randomly divided into two groups. The observation group (30 cases) was treated with speech therapy and acupuncture at Lianquan (CV 23), Jinjin (EX-HN 12), Yuye (EX-HN 13), Fengchi (GB 20), Yifeng (TE 17) and Wangu (GB 12) as major acupoints, while the control group (31 cases) was treated with speech therapy only. The changes of speech and acoustics indices were evaluated after 9 weeks treatment. RESULTS: The word articulation and correct rate of text of patients in two groups were both obviously improved after treatment (both P < 0.01). The total effective rate of 96.7% (29/30) in observation group was superior to that of 67.7% (21/31) in control group (P < 0.01). The maximum phonation time (MPT) of patients tested by aeromechanics analyzer were obviously prolonged in observation group (12 cases) and control group (11 cases) (both P < 0.01), and the improvement in observation group was more obvious (P < 0.01). CONCLUSION: Acupuncture combined with speech therapy can improve the effect on language and acoustics level for dysarthria.


Assuntos
Terapia por Acupuntura , Disartria/terapia , Acústica da Fala , Adulto , Idoso , Disartria/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fonoterapia , Adulto Jovem
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