Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 16 de 16
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Am Chem Soc ; 135(39): 14831-9, 2013 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-24044869

RESUMO

We report here the development of chemoenzymatic methods for the large-scale synthesis of cancer-associated antigens globopentaose (Gb5), fucosyl-Gb5 (Globo H), and sialyl-Gb5 (SSEA4) by using overexpressed glycosyltransferases coupled with effective regeneration of sugar nucleotides, including UDP-Gal, UDP-GalNAc, GDP-Fuc, and CMP-Neu5Ac. The enzymes used in the synthesis were first identified from different species through comparative studies and then overexpressed in E. coli and isolated for synthesis. These methods provide multigram quantities of products in high yield with only two or three purification steps and are suitable for the evaluation and development of cancer vaccines and therapeutics.


Assuntos
Antígenos Glicosídicos Associados a Tumores/metabolismo , Escherichia coli/genética , Glicosiltransferases/genética , Glicosiltransferases/metabolismo , Antígenos Glicosídicos Associados a Tumores/química , Clonagem Molecular , Glicosiltransferases/isolamento & purificação , Microbiologia Industrial , Regulação para Cima
2.
Invest New Drugs ; 30(1): 164-75, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20890633

RESUMO

Designed from a high throughput screened hit compound, novel 2-amino-1-thiazolyl imidazoles were synthesized and demonstrated cytotoxicity against human cancer cells. 1-(4-Phenylthiazol-2-yl)-4-(thiophen-2-yl)-1H-imidazol-2-amine (compound 2), a 2-amino-1-thiazolyl imidazole, inhibited tubulin polymerization, interacted with the colchicine-binding sites of tubulins, and caused cell cycle arrest at the G(2)/M phase in human gastric cancer cells. Disruption of the microtubule structure in cancer cells by compound 2 was also observed. Compound 2 concentration-dependently inhibited the proliferation of cancer cells in histocultured human gastric and colorectal tumors. Given orally, compound 2 prolonged the lifespans of leukemia mice intraperitoneally inoculated with the murine P388 leukemic cells. We report 2-amino-1-thiazolyl imidazoles as a novel class of orally active microtubule-destabilizing anticancer agents.


Assuntos
Antineoplásicos/administração & dosagem , Imidazóis/administração & dosagem , Neoplasias Experimentais/tratamento farmacológico , Tiazóis/administração & dosagem , Moduladores de Tubulina/administração & dosagem , Administração Oral , Animais , Antineoplásicos/síntese química , Antineoplásicos/metabolismo , Ligação Competitiva , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Colchicina/metabolismo , Relação Dose-Resposta a Droga , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Imidazóis/síntese química , Imidazóis/metabolismo , Concentração Inibidora 50 , Masculino , Camundongos , Camundongos Endogâmicos DBA , Camundongos Nus , Microtúbulos/efeitos dos fármacos , Microtúbulos/metabolismo , Estrutura Molecular , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Relação Estrutura-Atividade , Tiazóis/síntese química , Tiazóis/metabolismo , Fatores de Tempo , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/síntese química , Moduladores de Tubulina/metabolismo
3.
ACS Chem Biol ; 7(3): 481-6, 2012 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-22148723

RESUMO

In our effort to improve the efficiency and yield of xylose-to-ethanol bioconversion in Pichia stipitis, the transaldolase (TAL) in the pentose phosphate pathway was identified as a rate-limiting enzyme for improvement. A mutant containing the Q263R change was first obtained by directed evolution with 5-fold increase of activity, which was then incorporated into P. stipitesvia the pYDS vector to produce a genetically stable strain for fermentation on xylose. In comparison with the parental strain, TAL-Q263R(+) increases ethanol prodcution by 36% and 100% as measured by volumetric production rate and specific production rate, respectively. Thus improving the transaldolase activity in P. stipitis can significantly increase the rate and yield of xylose conversion to ethanol.


Assuntos
Etanol/metabolismo , Pichia/enzimologia , Engenharia de Proteínas , Transaldolase/metabolismo , Etanol/química , Conformação Molecular , Pichia/metabolismo , Transaldolase/genética , Xilose/química , Xilose/metabolismo
4.
Cancer Sci ; 102(1): 182-91, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21040217

RESUMO

BPR0C261 is a synthetic small molecule compound cytotoxic against human cancer cells and active prolonging the lifespan of leukemia mice. In the present study, we further investigated the mechanisms of its anticancer action and found that BPR0C261 inhibited microtubule polymerization through interacting with the colchicine binding sites on tubulins, disrupted microtubule arrangement and caused cell cycle arrest at G(2)/M phase in cancer cells. BPR0C261 also inhibited the clonogenic growths of cancer cells and showed cytotoxicity against human cervical cancer cells of multidrug-resistant phenotype. In addition, BPR0C261 concentration-dependently inhibited the proliferation and migration of HUVECs and disrupted the endothelial capillary-like tube formations in HUVEC and rat aorta ring cultures. Given orally, BPR0C261 inhibited angiogenesis in s.c. implanted Matrigel plugs in mice. Notably, its IC(50) values against the endothelial cell growths were approximately 10-fold lower than those against the cancer cells. It was found orally absorbable in mice and showed a good oral bioavailability (43%) in dogs. BPR0C261 permeated through the human intestinal Caco-2 cell monolayer, suggesting oral availability in humans. Orally absorbed BPR0C261 distributed readily into the s.c. xenografted tumors in nude mice in which the tumor tissue levels of BPR0C261 were found oral dose-dependent. BPR0C261 showed in vivo activities against human colorectal, gastric, and nasopharyngeal tumors in nude mice. Most interestingly, the combination of BPR0C261 plus cisplatin synergistically prolonged the lifespans of mice inoculated with murine leukemia cells. Thus, BPR0C261 is a novel orally active tubulin-binding antitumor agent with antimitotic, apoptosis-inducing, and vasculature disrupting activities.


Assuntos
Inibidores da Angiogênese/farmacologia , Antimitóticos/farmacologia , Antineoplásicos/farmacologia , Indóis/farmacologia , Tiazóis/farmacologia , Administração Oral , Animais , Antineoplásicos/farmacocinética , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cães , Humanos , Leucemia Experimental/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos , Microtúbulos/química , Microtúbulos/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
5.
J Med Chem ; 53(6): 2409-17, 2010 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-20170097

RESUMO

2-Amino-1-arylidenaminoimidazoles, a novel class of orally (po) active microtubule-destabilizing anticancer agents, were synthesized. The compounds were designed from a hit compound identified in a drug discovery platform by using cancer cell-based high throughput screening assay. Selective synthesized compounds exerted cell cytotoxicity against human cancer cells. The underlying mechanisms for the anticancer activity were demonstrated as interacting with the tubulins and inhibiting microtubule assembly, leading to proliferation inhibition and apoptosis induction in the human tumor cells. Furthermore, two compounds showed in vivo anticancer activities in both po and intravenously (iv) administered routes and prolonged the life spans of murine leukemic P388 cells-inoculated mice. These new po active antimitotic anticancer agents are to be further examined in preclinical studies and developed for clinical uses.


Assuntos
Antineoplásicos/farmacologia , Imidazóis/síntese química , Imidazóis/farmacologia , Neoplasias/tratamento farmacológico , Administração Oral , Animais , Antineoplásicos/administração & dosagem , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Humanos , Imidazóis/química , Concentração Inibidora 50 , Leucemia P388/tratamento farmacológico , Leucemia P388/patologia , Camundongos , Camundongos Endogâmicos DBA , Camundongos Nus , Microtúbulos/efeitos dos fármacos , Microtúbulos/metabolismo , Modelos Químicos , Estrutura Molecular , Neoplasias/patologia , Relação Estrutura-Atividade , Tubulina (Proteína)/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Proc Natl Acad Sci U S A ; 105(10): 3678-83, 2008 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-18319341

RESUMO

We describe a Nanostructure-Initiator Mass Spectrometry (NIMS) enzymatic (Nimzyme) assay in which enzyme substrates are immobilized on the mass spectrometry surface by using fluorous-phase interactions. This "soft" immobilization allows efficient desorption/ionization while also enabling the use of surface-washing steps to reduce signal suppression from complex biological samples, which results from the preferential retention of the tagged products and reactants. The Nimzyme assay is sensitive to subpicogram levels of enzyme, detects both addition and cleavage reactions (sialyltransferase and galactosidase), is applicable over a wide range of pHs and temperatures, and can measure activity directly from crude cell lysates. The ability of the Nimzyme assay to analyze complex mixtures is illustrated by identifying and directly characterizing beta-1,4-galactosidase activity from a thermophilic microbial community lysate. The optimal enzyme temperature and pH were found to be 65 degrees C and 5.5, respectively, and the activity was inhibited by both phenylethyl-beta-d-thiogalactopyranoside and deoxygalactonojirimycin. Metagenomic analysis of the community suggests that the activity is from an uncultured, unsequenced gamma-proteobacterium. In general, this assay provides an efficient method for detection and characterization of enzymatic activities in complex biological mixtures prior to sequencing or cloning efforts. More generally, this approach may have important applications for screening both enzymatic and inhibitor libraries, constructing and screening glycan microarrays, and complementing fluorous-phase organic synthesis.


Assuntos
Bioensaio/métodos , Espectrometria de Massas/métodos , Nanoestruturas , Sialiltransferases/metabolismo , beta-Galactosidase/metabolismo , Bactérias/efeitos dos fármacos , Bactérias/enzimologia , Inibidores Enzimáticos/farmacologia , Humanos , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Procedimentos Analíticos em Microchip , Especificidade por Substrato/efeitos dos fármacos , Temperatura
7.
Bioorg Med Chem ; 14(1): 83-91, 2006 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-16140536

RESUMO

Hepatitis C virus (HCV) infection is a severe liver disease that often leads to liver cirrhosis and hepatocellular carcinoma (HCC). Current therapy is inadequate to conquer this viral disease. In this study, we identified parthenolide (1), an active component in feverfew, a popular remedy for fever and migraine, as a lead compound with an EC50 value of 2.21 microM against HCV replication in a subgenomic RNA replicon assay system. Parthenolide is able to potentiate the interferon alpha-exerted anti-HCV effect. Several commercially available sesquiterpene lactones (2-5) structurally analogous to parthenolide and a series of synthesized Michael-type adducts of parthenolide (12-18) also exhibit micromolar concentrations for anti-HCV activities. Structure-activity relationship was elucidated to reveal that the spatial arrangement of the terpenoid skeleton fused with an alpha-methylene-gamma-lactone moiety produces maximal anti-HCV activity. In addition, a strong anti-HCV potency indicates a possibility of secondary amino adducts (12-18) converting back to parthenolide or being replaced by the nucleophilic residues of proteins inside cells. This work shows that screening of natural products is a viable and fast way for identifying novel molecular diversity as potential drug leads.


Assuntos
Hepacivirus/efeitos dos fármacos , Lactonas/síntese química , Lactonas/farmacologia , Replicon , Sesquiterpenos/síntese química , Sesquiterpenos/farmacologia , Northern Blotting , Genoma Viral , Hepacivirus/genética , Hepacivirus/fisiologia , Lactonas/química , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Sesquiterpenos/química , Espectrometria de Massas por Ionização por Electrospray
8.
Antimicrob Agents Chemother ; 49(10): 4197-202, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16189098

RESUMO

Chronic hepatitis C virus (HCV) infection is a worldwide health problem causing serious complications, such as liver cirrhosis and hepatoma. Alpha interferon (IFN-alpha) or its polyethylene glycol-modified form combined with ribavirin is the only recommended therapy. However, an alternative therapy is needed due to the unsatisfactory cure rate of the IFN-based therapy. Using a modified reporter assay based on the HCV subgenomic-replicon system, we found that sodium stibogluconate (SSG), a compound used for leishmania treatment, suppressed HCV replication. We have previously reported that SSG is effective at inhibiting HCV replication in a cell line permissive for HCV infection/replication and in an ex vivo assay using fresh human liver slices obtained from patients infected with HCV (26). In this study, we show that the SSG 50% inhibitory dose for HCV replication is 0.2 to 0.3 mg/ml (equivalent to 345 to 517 microM of Sb) in the HCV subgenomic-replicon system. We also found that SSG and IFN-alpha exert a strong synergistic anti-HCV effect in both the traditional isobologram analysis and the median effect principle (CalcuSyn analysis). The combination of SSG and IFN-alpha could sustain the antiviral response better than SSG or IFN-alpha alone. The results suggest that SSG may be a good drug candidate for use in combination with other therapeutics, such as IFN-alpha and ribavirin, to treat HCV infection.


Assuntos
Gluconato de Antimônio e Sódio/farmacologia , Antimônio/farmacologia , Antivirais/farmacologia , Cloretos/farmacologia , Hepacivirus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Genes Reporter , Proteínas de Fluorescência Verde/metabolismo , Hepacivirus/fisiologia , Humanos , Concentração Inibidora 50 , Cinética , Neoplasias Hepáticas/patologia , Luciferases/metabolismo
9.
J Virol Methods ; 129(2): 170-7, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16005986

RESUMO

Sip-L, a member of the Cupin superfamily, is a hepatic factor capable of supporting hepatitis C virus (HCV) replication in an otherwise non-permissive cell line. HCV-positive serum was used to infect Huh-7 and 293 cells stably expressing Sip-L. Using the culture medium of the infected cells as an infection source, sequential viral passages were carried out in both cell lines. Efficient viral passage was observed in 293-Sip-L cells but not in Huh-7-Sip-L cells. The viral concentrations in the culture medium increased gradually from less than 10(2) copies/mL to 5.3 x 10(4) copies/mL after 25 sequential passages in 293-Sip-L cells. Sequence analysis of the viral genomes obtained from both the initial and final inocula revealed emergence of mutation clusters in NS2, NS3, and NS5A coding regions. Immunofluorescence study revealed that only a small percentage of infected cells expressed a detectable level of viral protein. Caspase 3 activities in the infected cells increased progressively during the viral passages. In conclusion, perpetual propagation of HCV was achieved using Sip-L expressing cells, allowing for the development of mutation clusters in the genome. The mutant HCV can be used as an infection source to study the molecular mechanism of HCV replication.


Assuntos
Genoma Viral , Hepacivirus/fisiologia , Mutação , Caspase 3 , Caspases/metabolismo , Linhagem Celular/metabolismo , Linhagem Celular/virologia , Hepacivirus/genética , Humanos , Inoculações Seriadas , Proteínas não Estruturais Virais/genética , Replicação Viral
10.
Antimicrob Agents Chemother ; 48(8): 2876-82, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15273095

RESUMO

Hepatitis C virus (HCV) is a serious global problem, and present therapeutics are inadequate to cure HCV infection. In the present study, various antiviral assays show that As2O3 at submicromolar concentrations is capable of inhibiting HCV replication. The 50% effective concentration (EC50) of As2O3 required to inhibit HCV replication was 0.35 microM when it was determined by a reporter-based HCV replication assay, and the EC50 was below 0.2 microM when it was determined by quantitative reverse transcription-PCR analysis. As2O3 did not cause cellular toxicity at this concentration, as revealed by an MTS [3-(4,5-dimethylthiozol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] assay. A combination of As2O3 and alpha interferon exerted synergistic effects against HCV, as revealed by a multiple linear logistic model and isobologram analysis. Furthermore, in an alternative HCV antiviral system that may recapitulate additional steps involved in HCV infection and replication, As2O3 at 0.3 microM totally abolished the HCV signal, whereas alpha interferon at a high dose (5,000 IU/ml) only partially suppressed the HCV signal. The study highlights the indications for use of a novel class of anti-HCV agent. Further elucidation of the exact antiviral mechanism of As2O3 may lead to the development of agents with potent activities against HCV or related viruses.


Assuntos
Antivirais , Arsenicais/farmacologia , Hepacivirus/efeitos dos fármacos , Óxidos/farmacologia , Replicação Viral/efeitos dos fármacos , Trióxido de Arsênio , Northern Blotting , Western Blotting , Linhagem Celular , Avaliação Pré-Clínica de Medicamentos , Sinergismo Farmacológico , Genes Reporter , Hepacivirus/fisiologia , Humanos , Interferon-alfa/farmacologia , RNA Viral/análise , RNA Viral/biossíntese , Replicon/efeitos dos fármacos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
11.
Antimicrob Agents Chemother ; 48(7): 2693-6, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15215127

RESUMO

Antiviral agents are urgently needed to fight severe acute respiratory syndrome (SARS). We showed that niclosamide, an existing antihelminthic drug, was able to inhibit replication of a newly discovered coronavirus, SARS-CoV; viral antigen synthesis was totally abolished at a niclosamide concentration of 1.56 microM, as revealed by immunoblot analysis. Thus, niclosamide represents a promising drug candidate for the effective treatment of SARS-CoV infection.


Assuntos
Anti-Helmínticos/farmacologia , Antivirais , Niclosamida/farmacologia , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Animais , Chlorocebus aethiops , Imunofluorescência , Células Vero
12.
J Virol Methods ; 116(1): 27-33, 2004 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-14715304

RESUMO

Hepatitis C virus (HCV) encodes a polyprotein that needs to be processed proteolytically by cellular and viral proteases into mature functional proteins. One of the viral proteins, NS3/4A, has serine protease activity that is critical for virus maturation. The generation and characterization of an engineered HCV replicon cell line (Ava5) is described which constitutively expresses EGdelta4AB)SEAP reporter protein and the cell line was designated as Ava5-EG(delta4AB)SEAP. EG(delta4AB)SEAP is a fusion protein in which Enhanced Green Fluorescent Protein (EGFP) was fused to SEcreted Alkaline Phosphatase (SEAP) through the NS3/4A protease decapeptide recognition sequence, delta4AB, which spans the NS4A and NS4B junction region. The secretion of SEAP into culture medium has been shown to depend on the cleavage of delta4AB by HCV NS3/4A protease. It is demonstrated that the amount of NS3/4A in Ava5-EG(delta4AB)SEAP cells correlated well with the copy numbers of HCV subgenomic RNA. It is also shown that replication of HCV subgenomic RNA inside cells is reflected by the alkaline phosphatase (SEAP) levels in culture medium. SEAP activity in the culture medium of Ava5-EG(delta4AB)SEAP was approximately 50-fold higher than the parental Ava5 cells. Ava5-EG(delta4AB)SEAP was validated as a drug screening system since several known HCV inhibitors were shown to reduce SEAP activities in culture media of Ava5-EG(delta4AB)SEAP cells. In conclusion, Ava5-EG(delta4AB)SEAP cells can be used to monitor HCV sub-genomic replication and the assay can be readily adapted to high throughput screening format to identify prospective anti-HCV drugs.


Assuntos
Antivirais/farmacologia , Avaliação Pré-Clínica de Medicamentos/métodos , Hepacivirus/efeitos dos fármacos , Replicon , Replicação Viral/efeitos dos fármacos , Fosfatase Alcalina/genética , Linhagem Celular , Meios de Cultura/química , Proteínas de Fluorescência Verde , Hepacivirus/crescimento & desenvolvimento , Humanos , Interferon-alfa/farmacologia , Interferon gama/farmacologia , Proteínas Luminescentes , Proteínas Recombinantes de Fusão/metabolismo , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismo , Inibidores de Serina Proteinase/farmacologia , Tosilfenilalanil Clorometil Cetona/farmacologia , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/fisiologia , Proteínas Virais/genética , Proteínas Virais/fisiologia
13.
Biochem Biophys Res Commun ; 310(2): 537-41, 2003 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-14521943

RESUMO

Using a hepatitis C virus (HCV) subgenomic RNA replicon system, drugs currently being used to treat other human diseases were examined for their antiviral activities against HCV. Several drugs including sodium stibogluconate, a compound used to treat leishmaniasis, were capable of suppressing replication of HCV replicon. The antiviral effect of sodium stibogluconate was subsequently verified using a cell line (293EBNA-Sip-L) previously proved to be permissive for HCV infection/replication. An ex vivo assay using fresh human liver slices established and a panel of human liver slices was obtained from biopsy samples of patients infected with HCV was used to examine the antiviral activity of this drug. A nearly complete suppression effect was achieved in four of six human liver slices at the drug concentration of 100 microg/ml, lower than what was required to treat leishmaniasis. A human trial is mandatory to understand its clinical value in treating chronic hepatitis C.


Assuntos
Gluconato de Antimônio e Sódio/farmacologia , Antivirais/farmacologia , Hepacivirus/efeitos dos fármacos , Adulto , Idoso , Linhagem Celular , Sobrevivência Celular , Células Cultivadas , Feminino , Hepacivirus/fisiologia , Hepatócitos/citologia , Humanos , Interferons/farmacologia , Fígado/virologia , Masculino , Pessoa de Meia-Idade , Replicação Viral/efeitos dos fármacos
14.
J Med Chem ; 46(9): 1706-15, 2003 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-12699388

RESUMO

A series of N-heterocyclic indolyl glyoxylamides were synthesized and evaluated for in vitro and in vivo anticancer activities. They exhibited a broad spectrum of anticancer activity not only in murine leukemic cancer cells but also in human gastric, breast, and uterus cancer cells as well as their multidrug resistant sublines with a wide range of IC(50) values. They also induced apoptosis and caused DNA fragmentation in human gastric cancer cells. Among the compounds studied, 7 showed the most potent activity of growth inhibition (IC(50) = 17-1711 nM) in several human cancer cells. Given orally, compounds 7 and 13 dose-dependently prolonged the survival of animals inoculated with P388 leukemic cancer cells. N-Heterocyclic indolyl glyoxylamides may be useful as orally active chemotherapeutic agents against cancer and refractory cancerous diseases of multidrug resistance phenotype.


Assuntos
Antineoplásicos/síntese química , Glioxilatos/síntese química , Indóis/síntese química , Tiazóis/síntese química , Administração Oral , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose , Divisão Celular/efeitos dos fármacos , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Glioxilatos/química , Glioxilatos/farmacologia , Humanos , Indóis/química , Indóis/farmacologia , Leucemia P388/mortalidade , Camundongos , Camundongos Endogâmicos DBA , Transplante de Neoplasias , Relação Estrutura-Atividade , Tiazóis/química , Tiazóis/farmacologia , Células Tumorais Cultivadas
15.
Org Lett ; 4(3): 463-6, 2002 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-11820905

RESUMO

A facile VO(acac)(2)-catalyzed in situ generation of iminium ions from amine N-oxides and their participation in a modified Mannich-type reaction is described.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...