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1.
Chem Commun (Camb) ; 58(46): 6653-6656, 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35593224

RESUMO

A Cu-catalyzed asymmetric 1,6-conjugate addition of in situ generated para-quinone methides (p-QMs) with ß-ketoester has been developed to construct a ketoester skeleton bearing an adjacent tertiary-quaternary carbon stereocenter in good yields and high enantioselectivities. This is the first example of metal-catalyzed asymmetric transformations of the in situ generated p-QMs, avoiding using pre-synthesized p-QMs requiring bulky 2,6-substitutions and highlighting a new dual catalytic activation with the chiral bis(oxazoline)-metal complex acting as a normal Lewis acid to activate the ß-ketoesters and a source of Brønsted acid responsible for generating the p-QMs in situ.


Assuntos
Cobre , Indolquinonas , Catálise , Metais
2.
Org Biomol Chem ; 19(30): 6588-6592, 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34023869

RESUMO

Using visible light as a driving force and molecular oxygen as a green oxidant, we developed bis(oxazoline)-Ni(acac)2 catalyzed asymmetric α-hydroxylation of ß-keto esters under low photosensitizer loading, and the protocol enabled an efficient transformation to provide the desired chiral α-hydroxy-ß-keto esters in high yields (up to 99%) and enantioselectivities (up to 99% ee) at room temperature.

3.
J Org Chem ; 85(15): 9491-9502, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32692168

RESUMO

The functionalization of indoles in the carbocyclic ring has been achieved via organocatalytic enantioselective Friedel-Crafts benzhydrylation of hydroxyindoles with in situ generated ortho-quinomethanes in oil-water biphases, allowing an efficient access to varied diarylindolylmethanes with a wide substrate scope. The high yields, excellent stereoselectivities, mild conditions, low catalyst loading, and easy scalability also demonstrated the interest of this novel methodology.

4.
Org Biomol Chem ; 18(26): 4927-4931, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32573633

RESUMO

A highly enantioselective homogeneous fluorination of cyclic ß-keto esters catalyzed by diphenylamine linked bis(oxazoline)-Cu(OTf)2 complexes has been established in a continuous flow microreactor. The microreactor allowed an efficient transformation with reaction times ranging from 0.5 to 20 min, and the desired products were afforded in high yields (up to 99%) with excellent enantioselectivities (up to 99% ee) at a low catalyst loading of 1 mol%.

5.
Drug Des Devel Ther ; 14: 1663-1681, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32431491

RESUMO

Anaplastic lymphoma kinase (ALK) inhibitors are important treatment options for non-small-cell lung cancer (NSCLC), associated with ALK gene rearrangement. Patients with ALK gene rearrangement show sensitivity to and benefit clinically from treatment with ALK tyrosine kinase inhibitors (ALK-TKIs). To date, crizotinib, ceritinib, alectinib, brigatinib, lorlatinib, and entrectinib have received approval from the US Food and Drug Administration and/or the European Medicines Agency for use during the treatment of ALK-gene-rearrangement forms of NSCLC. Although the oral route of administration is convenient and results in good compliance among patients, oral administration can be affected by many factors, such as food, intragastric pH, cytochrome P450 enzymes, transporters, and p-glycoprotein. These factors can result in increased risks for serious adverse events or can lead to reduced therapeutic effects of ALK-TKIs. This review characterizes and summarizes the pharmacokinetic parameters and drug--drug interactions associated with ALK-TKIs to provide specific recommendations for oncologists and clinical pharmacists when prescribing ALK-TKIs.


Assuntos
Quinase do Linfoma Anaplásico/antagonistas & inibidores , Antineoplásicos/farmacocinética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Inibidores de Proteínas Quinases/farmacocinética , Quinase do Linfoma Anaplásico/genética , Quinase do Linfoma Anaplásico/metabolismo , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/patologia , Interações Medicamentosas , Humanos , Neoplasias Pulmonares/patologia , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos
6.
Org Biomol Chem ; 18(13): 2398-2404, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32191253

RESUMO

A highly regioselective and enantioselective N-alkylation of isoxazol-5-ones with para-quinone methides promoted by bi-functional squaramide catalysts was developed. This unexpected asymmetric N-addition of isoxazolinones afforded a series of enantioenriched N-diarylmethane substituted isoxazolinones with high yields and enantioselectivities (up to 97 : 3 er). This reaction not only provides a useful approach for intermolecular chiral C-N bond formation but also demonstrates the immense potential of isoxazol-5-ones as N-nucleophiles in catalytic asymmetric reactions.

7.
Onco Targets Ther ; 12: 4859-4868, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417283

RESUMO

Background: The present standard dose of gemcitabine (Gem), a pyrimidine antimetabolite, is 1,000-1,250 mg/m2, and the infusion time is 30 min. However, pharmacological studies have demonstrated that Gem with prolonged infusion could attain a better accumulation rate of Gem triphosphate (active metabolites of Gem), indicating that Gem with prolonged infusion is superior to 30-min infusion. Thus, this systematic review aims to provide some references for Gem administered as a prolonged infusion. Methods: We searched electronic databases, including PubMed, EMBASE, Cochrane Library, and CNKI, for trials. Keywords were "Gem," "prolonged infusion," and "low-dose." In addition, we used the Cochrane Handbook V5.1.0 and methodological index for non-randomized studies to evaluate the quality of randomized controlled trials (RCTs) and non-RCTs, respectively. Furthermore, Cochrane Collaboration guidelines and the PRISMA statement were adopted. Results: We systematically reviewed 19 studies (5 RCTs and 14 non-RCTs). All studies assessed the efficacy and safety of Gem administered as a prolonged low-dose infusion (P-LDI) and reported that Gem administered as P-LDI was effective and well tolerated. Conclusion: Gem administered as P-LDI is effective, safe, and economical, especially suited for patients with poor performance status or without good economic condition.

8.
Org Biomol Chem ; 16(41): 7702-7710, 2018 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-30288521

RESUMO

A highly enantioselective fluorination of indanone-2-carboxylates catalyzed by a polystyrene-supported diphenylamine-linked bis(oxazoline) (PS-box)-Cu(OTf)2 complex has been developed in a continuous flow system. The supported complex exhibited extremely efficient catalytic performance with high activity, affording the corresponding products in excellent yields (up to 99% yield) with excellent enantioselectivities (up to 99% ee) and more than 4000 turnover number (TON).

9.
Org Biomol Chem ; 15(19): 4191-4198, 2017 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-28443921

RESUMO

A highly enantioselective conjugate addition of 2-substituted benzofuran-3(2H)-ones to α,ß-unsaturated ketones promoted by chiral copper complexes has been developed, affording the Michael addition products with quaternary stereocenters in good to high yields (up to 95% yield) with excellent enantioselectivities (up to 99% ee). The chiral Michael adducts could be readily converted to the polycyclic benzofuran-type framework via the Robinson annulation.

10.
Biosens Bioelectron ; 52: 281-7, 2014 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-24071363

RESUMO

Using structural characterizations and electrochemical measurements, we explored and investigated the effect of the structure of enzyme electrodes with glucose oxidase (GOD) that were modified by reduced graphene oxide (rGO) sheets. The rGO sheets with different defect density, layers, and oxygen concentrations were chosen to modify the enzyme electrode, and all the modified enzyme electrodes exhibited excellent electrocatalytic activities and performances towards glucose. The abundant defects in rGO induce easy absorption of GOD. At a low oxygen concentration, rGO sheets help to induce the direct electron transfer (DET) on the rGO-modified electrode, and at a higher oxygen concentration, the reduction of H2O2 occurred instead of DET on the surface of the rGO-modified electrode. When rGO modified the enzyme electrode under the working model of H2O2 reduction, an increase in the number of the oxygen functional groups could lead to an increase in the absorption of GOD, resulting in the improvement of the affinity and sensitivity of the biosensor. The rGO-modified enzyme electrode can provide faster response, higher sensitivity, and better affinity by optimizing and controlling the structure of graphene and its derivatives.


Assuntos
Técnicas Biossensoriais/métodos , Glucose/isolamento & purificação , Grafite/química , Eletroquímica , Eletrodos , Enzimas Imobilizadas/química , Glucose/química , Glucose Oxidase/química , Peróxido de Hidrogênio/química , Óxidos/química
11.
Acta Biochim Biophys Sin (Shanghai) ; 44(6): 490-502, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22551583

RESUMO

Angiogenesis inhibitors combined with chemotherapeutic drugs have significant efficacy in the treatment of a variety of cancers. Pseudolarix acid B (PAB) is a traditional pregnancy-terminating agent, which has previously been shown to reduce tumor growth and angiogenesis. In this study, we used the high content screening assay to examine the effects of PAB on human umbilical vein endothelial cells (HUVECs). Two hepatocarcinoma 22-transplanted mouse models were used to determine PAB efficacy in combination with 5-fluorouracil (5-Fu). Our results suggested that PAB (0.156-1.250 µM) inhibited HUVECs motility in a concentration-dependent manner without obvious cytotoxicity in vitro. In vivo, PAB (25 mg/kg/day) promoted the anti-tumor efficacy of 5-Fu (5 mg/kg/2 days) in combination therapy, resulting in significantly higher tumor inhibition rates, lower microvessel density values, and prolonged survival times. It was also demonstrated that PAB acted by blocking the cell cycle at both the G(1)/S boundary and M phase, down-regulation of vascular endothelial growth factor, hypoxia-inducible factor 1α and cyclin E expression, and up-regulation of cdc2 expression. These observations provide the first evidence that PAB in combination with 5-Fu may be useful in cancer treatment.


Assuntos
Diterpenos/farmacologia , Fluoruracila/farmacologia , Inibidores da Angiogênese/farmacologia , Animais , Pontos de Checagem do Ciclo Celular , Movimento Celular/efeitos dos fármacos , Diterpenos/administração & dosagem , Fluoruracila/administração & dosagem , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos , Neovascularização Patológica/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Front Biosci ; 11: 2113-22, 2006 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-16720298

RESUMO

Metallothionein (MT), a metal-binding protein induced primarily by heavy metals in vertebrates, is considered a biomarker for environmental heavy-metal contamination. To investigate heavy metal pollution in the freshwater environment, MT-I and MT-II were purified from livers of crucian carp (Carassius carassius) by gel exclusion chromatography and ion exchange chromatography. To detect the purified MT-II, a specific monoclonal antibody (mAb) against crucian carp MT-II was produced from the hybridoma strains by cell-cell fusion. By using Enzyme-Linked Immunosorbent Assay (ELISA) with this mAb, the purified crucian carp MT-II was detected with a high specificity and sensitivity. There was a good correlation between the amount of MT-II in carp livers and the concentration of heavy metals in water. ELISA was then used to evaluated the degree of heavy metal pollution in two freshwater systems. The results indicate that the MT-II content in carp liver tissue can be used as an indicator of environmental heavy-metal pollution.


Assuntos
Biomarcadores/análise , Ensaio de Imunoadsorção Enzimática/métodos , Metalotioneína/análise , Metais Pesados/análise , Poluentes da Água/análise , Animais , Anticorpos Monoclonais , Carpas , Monitoramento Ambiental/métodos , Fígado/química , Metalotioneína/metabolismo , Metais Pesados/metabolismo , Espectrofotometria Atômica , Poluentes da Água/metabolismo
13.
Biochem Biophys Res Commun ; 342(4): 1297-304, 2006 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-16516146

RESUMO

The genomic DNA of crucian carp (Carassius cuvieri) metallothionein-II (ccMT-II), with its upstream region, was obtained. The sequence analysis of its upstream region revealed several putative cis-acting elements including seven metal regulatory elements (MREs), three activator protein 1 (AP1), two glucocorticoid response elements (GREs), etc. The seven MREs locate into two clusters, a distal cluster with four MREs within -800/-600bp from the translation start site and a proximal cluster with three MREs close to TATA box. In transient luciferase gene expression assays, both of the distal and proximal cluster MREs have significantly shown synergistic effects in the transcription of ccMT-II gene; the proximal cluster of MREs serves as the major elements in metal inducing activity; Zn(2+) and Cd(2+) served as much stronger inducers than Cu(2+) shown in ccMT-II expression. The two GRE homologous sequences in ccMT-II promoter showed not to be inductive in either HepG2 or HEK293.


Assuntos
Carpas/genética , Clonagem Molecular , Metalotioneína/genética , Regiões Promotoras Genéticas/genética , Animais , Sequência de Bases , Células Cultivadas , Dados de Sequência Molecular , Homologia de Sequência do Ácido Nucleico
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